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    AuthorTitleYearJournal/ProceedingsReftypeDOI/URL
    Abel, T., Nguyen, P., Barad, M., Deuel, T. & Kandel, E. Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory {1997} CELL
    Vol. {88}({5}), pp. {615-626} 
    article  
    Abstract: To explore the role of protein kinase A (PKA) in the late phase of long-term potentiation (L-LTP) and memory, we generated transgenic mice that express R(AB), an inhibitory form of the regulatory subunit of PKA, only in the hippocampus and other forebrain regions by using the promoter from the gene encoding Ca2+/calmodulin protein kinase II alpha. In these R(AB) transgenic mice, hippocampal PKA activity was reduced, and L-LTP was significantly decreased in area CA1, without affecting basal synaptic transmission or the early phase of LTP. Moreover, the L-LTP deficit was paralleled by behavioral deficits in spatial memory and in long-term but not short-term memory for contextual fear conditioning. These deficits in long-term memory were similar to those produced by protein synthesis inhibition. Thus, PKA plays a critical role in the consolidation of long-term memory.
    BibTeX:
    @article{Abel1997,
      author = {Abel, T and Nguyen, PV and Barad, M and Deuel, TAS and Kandel, ER},
      title = {Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory},
      journal = {CELL},
      publisher = {CELL PRESS},
      year = {1997},
      volume = {88},
      number = {5},
      pages = {615-626}
    }
    
    Abell, F., Krams, M., Ashburner, J., Passingham, R., Friston, K., Frackowiak, R., Happe, F., Frith, C. & Frith, U. The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans {1999} NEUROREPORT
    Vol. {10}({8}), pp. {1647-1651} 
    article  
    Abstract: AUTISM is a biological disorder which affects social cognition, and understanding brain abnormalities of the former will elucidate the brain basis of the latter. We report structural MRI data on 15 high-functioning individuals with autistic disorder. A voxel-based whole brain analysis identified grey matter differences in an amygdala centered system relative to 15 age- and IQ-matched controls. Decreases of grey matter were found in anterior parts of this system (right paracingulate sulcus, left inferior frontal gyrus). Increases were found in posterior parts (amygdala/peri-amygdaloid cortex, middle temporal gyrus, inferior temporal gyrus), and in regions of the cerebellum. These structures are implicated in social cognition by animal, imaging and histopathological studies. This study therefore provides converging evidence of the physiological basis of social cognition. NeuroReport 10:1647-1651 (C) 1999 Lippincott Williams & Wilkins.
    BibTeX:
    @article{Abell1999,
      author = {Abell, F and Krams, M and Ashburner, J and Passingham, R and Friston, K and Frackowiak, R and Happe, F and Frith, C and Frith, U},
      title = {The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans},
      journal = {NEUROREPORT},
      publisher = {LIPPINCOTT WILLIAMS & WILKINS},
      year = {1999},
      volume = {10},
      number = {8},
      pages = {1647-1651}
    }
    
    Adolphs, R. Cognitive neuroscience of human social behaviour {2003} NATURE REVIEWS NEUROSCIENCE
    Vol. {4}({3}), pp. {165-178} 
    article DOI  
    Abstract: We are an intensely social species - it has been argued that our social nature defines what makes us human, what makes us conscious or what gave us our large brains. As a new field, the social brain sciences are probing the neural underpinnings of social behaviour and have produced a banquet of data that are both tantalizing and deeply puzzling. We are finding new links between emotion and reason, between action and perception, and between representations of other people and ourselves. No less important are the links that are also being established across disciplines to understand social behaviour, as neuroscientists, social psychologists, anthropologists, ethologists and philosophers forge new collaborations.
    BibTeX:
    @article{Adolphs2003,
      author = {Adolphs, R},
      title = {Cognitive neuroscience of human social behaviour},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2003},
      volume = {4},
      number = {3},
      pages = {165-178},
      doi = {{10.1038/nrn1056}}
    }
    
    Adolphs, R. Neural systems for recognizing emotion {2002} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {12}({2}), pp. {169-177} 
    article  
    Abstract: Recognition of emotion draws on a distributed set of structures that include the occipitotemporal neocortex, amygdala, orbitofrontal cortex and right frontoparietal cortices. Recognition of fear may draw especially on the amygdala and the detection of disgust may rely on the insula and basal ganglia. Two important mechanisms for recognition of emotions are the construction of a simulation of the observed emotion in the perceiver, and the modulation of sensory cortices via top-down influences.
    BibTeX:
    @article{Adolphs2002,
      author = {Adolphs, R},
      title = {Neural systems for recognizing emotion},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      publisher = {CURRENT BIOLOGY LTD},
      year = {2002},
      volume = {12},
      number = {2},
      pages = {169-177}
    }
    
    Adolphs, R. The neurobiology of social cognition {2001} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {11}({2}), pp. {231-239} 
    article  
    Abstract: Recent studies have begun to elucidate the roles played in social cognition by specific neural structures, genes, and neurotransmitter systems. Cortical regions in the temporal robe participate in perceiving socially relevant stimuli, whereas the amygdala, right somatosensory cortices, orbitofrontal cortices, and cingulate cortices all participate in linking perception of such stimuli to motivation, emotion, and cognition. Open questions remain about the domain-specificity of social cognition, about its overlap with emotion and with communication, and about the methods best suited for its investigation.
    BibTeX:
    @article{Adolphs2001,
      author = {Adolphs, R},
      title = {The neurobiology of social cognition},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      publisher = {CURRENT BIOLOGY LTD},
      year = {2001},
      volume = {11},
      number = {2},
      pages = {231-239}
    }
    
    Adolphs, R. Social cognition and the human brain {1999} TRENDS IN COGNITIVE SCIENCES
    Vol. {3}({12}), pp. {469-479} 
    article  
    Abstract: Humans are exceedingly social animals, but the neural underpinnings of social cognition and behavior are not well understood. Studies in humans and other primates have pointed to several structures that play a key role in guiding social behaviors: the amygdala, ventromedial frontal cortices, and right somatosensory-related cortex, among others. These structures appear to mediate between perceptual representations of socially relevant stimuli, such as the sight of conspecifics, and retrieval of knowledge (or elicitation of behaviors) that such stimuli can trigger. Current debates concern the extent to which social cognition draws upon processing specialized for social information, and the relative contributions made to social cognition by innate and acquired knowledge.
    BibTeX:
    @article{Adolphs1999,
      author = {Adolphs, R},
      title = {Social cognition and the human brain},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {1999},
      volume = {3},
      number = {12},
      pages = {469-479}
    }
    
    Adolphs, R., Damasio, H., Tranel, D., Cooper, G. & Damasio, A. A role for somatosensory cortices in the visual recognition of emotion as revealed by three-dimensional lesion mapping {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({7}), pp. {2683-2690} 
    article  
    Abstract: Although lesion and functional imaging studies have broadly implicated the right hemisphere in the recognition of emotion, neither the underlying processes nor the precise anatomical correlates are well understood. We addressed these two issues in a quantitative study of 108 subjects with focal brain lesions, using three different tasks that assessed the recognition and naming of six basic emotions from facial expressions. Lesions were analyzed as a function of task performance by coregistration in a common brain space, and statistical analyses of their joint volumetric density revealed specific regions in which damage was significantly associated with impairment. We show that recognizing emotions from visually presented facial expressions requires right somatosensory-related cortices. The findings are consistent with the idea that we recognize another individual's emotional state by internally generating somatosensory representations that simulate how the other individual would feel when displaying a certain facial expression. Follow-up experiments revealed that conceptual knowledge and knowledge of the name of the emotion draw on neuroanatomically separable systems. Right somatosensory-related cortices thus constitute an additional critical component that functions together with structures such as the amygdala and right visual cortices in retrieving socially relevant information from faces.
    BibTeX:
    @article{Adolphs2000,
      author = {Adolphs, R and Damasio, H and Tranel, D and Cooper, G and Damasio, AR},
      title = {A role for somatosensory cortices in the visual recognition of emotion as revealed by three-dimensional lesion mapping},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {7},
      pages = {2683-2690}
    }
    
    Adolphs, R., Damasio, H., Tranel, D. & Damasio, A. Cortical systems for the recognition of emotion in facial expressions {1996} JOURNAL OF NEUROSCIENCE
    Vol. {16}({23}), pp. {7678-7687} 
    article  
    Abstract: This study is part of an effort to map neural systems involved in the Processing of emotion, and it focuses on the possible cortical components of the process of recognizing facial expressions. We hypothesized that the cortical systems most responsible for the recognition of emotional facial expressions would draw on discrete regions of right higher-order sensory cortices and that the recognition of specific emotions would depend on partially distinct system subsets of such cortical regions. We tested these hypotheses using lesion analysis in 37 subjects with focal brain damage. Subjects were asked to recognize facial expressions of six basic emotions: happiness, surprise, fear, anger, disgust, and sadness. Data were analyzed with a novel technique, based on three-dimensional reconstruction of brain images, in which anatomical description of surface lesions and task performance scores were jointly mapped onto a standard brain-space. We found that all subjects recognized happy expressions normally but that some subjects were impaired in recognizing negative emotions, especially fear and sadness. The cortical surface regions that best correlated with impaired recognition of emotion were in the right inferior parietal cortex and in the right mesial anterior infracalcarine cortex. We did not find impairments in recognizing any emotion in subjects with lesions restricted to the left hemisphere. These data provide evidence for a neural system important to processing facial expressions of some emotions, involving discrete visual and somatosensory cortical sectors in right hemisphere.
    BibTeX:
    @article{Adolphs1996,
      author = {Adolphs, R and Damasio, H and Tranel, D and Damasio, AR},
      title = {Cortical systems for the recognition of emotion in facial expressions},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1996},
      volume = {16},
      number = {23},
      pages = {7678-7687}
    }
    
    Adolphs, R., Gosselin, F., Buchanan, T., Tranel, D., Schyns, P. & Damasio, A. A mechanism for impaired fear recognition after amygdala damage {2005} NATURE
    Vol. {433}({7021}), pp. {68-72} 
    article DOI  
    Abstract: Ten years ago, we reported that SM, a patient with rare bilateral amygdala damage, showed an intriguing impairment in her ability to recognize fear from facial expressions(1). Since then, the importance of the amygdala in processing information about facial emotions has been borne out by a number of lesion(2-4) and functional imaging studies(5,6). Yet the mechanism by which amygdala damage compromises fear recognition has not been identified. Returning to patient SM, we now show that her impairment stems from an inability to make normal use of information from the eye region of faces when judging emotions, a defect we trace to a lack of spontaneous fixations on the eyes during free viewing of faces. Although SM fails to look normally at the eye region in all facial expressions, her selective impairment in recognizing fear is explained by the fact that the eyes are the most important feature for identifying this emotion. Notably, SM's recognition of fearful faces became entirely normal when she was instructed explicitly to look at the eyes. This finding provides a mechanism to explain the amygdala's role in fear recognition, and points to new approaches for the possible rehabilitation of patients with defective emotion perception.
    BibTeX:
    @article{Adolphs2005,
      author = {Adolphs, R and Gosselin, F and Buchanan, TW and Tranel, D and Schyns, P and Damasio, AR},
      title = {A mechanism for impaired fear recognition after amygdala damage},
      journal = {NATURE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2005},
      volume = {433},
      number = {7021},
      pages = {68-72},
      doi = {{10.1038/nature03086}}
    }
    
    Adolphs, R., Tranel, D. & Damasio, A. The human amygdala in social judgment {1998} NATURE
    Vol. {393}({6684}), pp. {470-474} 
    article  
    Abstract: Studies in animals have implicated the amygdala in emotional(1-3) and social(4-6) behaviours, especially those related to fear and aggression. Although lesion(7-10) and functional imaging(11-13) studies in humans have demonstrated the amygdala's participation in recognizing emotional facial expressions, its role in human social behaviour has remained unclear. We report here our investigation into the hypothesis that the human amygdala is required for accurate social judgments of other individuals on the basis of their facial appearance. We asked three subjects with complete bilateral amygdala damage to judge faces of unfamiliar people with respect to two attributes important in real-life social encounters: approachability and trustworthiness. All three subjects judged unfamiliar individuals to be more approachable and more trustworthy than did control subjects. The impairment was most striking for faces to which normal subjects assign the most negative ratings: unapproachable and untrustworthy looking individuals. Additional investigations revealed that the impairment does not extend to judging verbal descriptions of people. The amygdala appears to be an important component of the neural systems that help retrieve socially relevant knowledge on the basis of facial appearance.
    BibTeX:
    @article{Adolphs1998,
      author = {Adolphs, R and Tranel, D and Damasio, AR},
      title = {The human amygdala in social judgment},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1998},
      volume = {393},
      number = {6684},
      pages = {470-474}
    }
    
    ADOLPHS, R., TRANEL, D., DAMASIO, H. & DAMASIO, A. FEAR AND THE HUMAN AMYGDALA {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({9}), pp. {5879-5891} 
    article  
    Abstract: We have previously reported that bilateral amygdala damage in humans compromises the recognition of fear in facial expressions while leaving intact recognition of face identity (Adolphs et al., 1994). The present study aims at examining questions motivated by this finding. We addressed the possibility that unilateral amygdala damage might be sufficient to impair recognition of emotional expressions. We also obtained further data on our subject with bilateral amygdala damage, in order to elucidate possible mechanisms that could account for the impaired recognition of expressions of fear. The results show that bilateral, but not unilateral, damage to the human amygdala impairs the processing of fearful facial expressions. This impairment appears to result from an insensitivity to the intensity of fear expressed by faces. We also confirmed a double dissociation between the recognition of facial expressions of fear, and the recognition of identity of a face: these two processes can be impaired independently, lending support to the idea that they are subserved in part by anatomically separate neural systems. Based on our data, and on what is known about the amygdala's connectivity, we propose that the amygdala is required to link visual representations of facial expressions, on the one hand, with representations that constitute the concept of fear, on the other. Preliminary data suggest the amygdala's role extends to both recognition and recall of fearful facial expressions.
    BibTeX:
    @article{ADOLPHS1995,
      author = {ADOLPHS, R and TRANEL, D and DAMASIO, H and DAMASIO, AR},
      title = {FEAR AND THE HUMAN AMYGDALA},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1995},
      volume = {15},
      number = {9},
      pages = {5879-5891}
    }
    
    ADOLPHS, R., TRANEL, D., DAMASIO, H. & DAMASIO, A. IMPAIRED RECOGNITION OF EMOTION IN FACIAL EXPRESSIONS FOLLOWING BILATERAL DAMAGE TO THE HUMAN AMYGDALA {1994} NATURE
    Vol. {372}({6507}), pp. {669-672} 
    article  
    Abstract: STUDIES in animals have shown that the amygdala receives highly processed visual input(1,2), contains neurons that respond selectively to faces(3), and that it participates in emotion(4,5) and social behaviour(6). Although studies in epileptic patients support its role in emotion(7), determination of the amygdala's function in humans has been hampered by the rarity of patients with selective amygdala lesions(8). Here, with the help of one such rare patient, we report findings that suggest the human amygdala may be indispensable to: (1) recognize fear in facial expressions; (2) recognize multiple emotions in a single facial expression; but (3) is not required to recognize personal identity from faces. These results suggest that damage restricted to the amygdala causes very specific recognition impairments, and thus constrains the broad notion that the amygdala is involved in emotion.
    BibTeX:
    @article{ADOLPHS1994,
      author = {ADOLPHS, R and TRANEL, D and DAMASIO, H and DAMASIO, A},
      title = {IMPAIRED RECOGNITION OF EMOTION IN FACIAL EXPRESSIONS FOLLOWING BILATERAL DAMAGE TO THE HUMAN AMYGDALA},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1994},
      volume = {372},
      number = {6507},
      pages = {669-672}
    }
    
    Adolphs, R., Tranel, D., Hamann, S., Young, A., Calder, A., Phelps, E., Anderson, A., Lee, G. & Damasio, A. Recognition of facial emotion in nine individuals with bilateral amygdala damage {1999} NEUROPSYCHOLOGIA
    Vol. {37}({10}), pp. {1111-1117} 
    article  
    Abstract: Findings from several case studies have shown that bilateral amygdala damage impairs recognition of emotions in facial expressions, especially fear. However, one study did not find such an impairment, and, in general, comparison across studies has been made difficult because of the different stimuli and tasks employed. In a collaborative study to facilitate such comparisons, we report here the recognition of emotional facial expressions in nine subjects with bilateral amygdala damage, using a sensitive and quantitative assessment. Compared to controls, the subjects as a group were significantly impaired in recognizing fear, although individual performances ranged from severely impaired to essentially normal. Most subjects were impaired on several negative emotions in addition to fear, but no subject was impaired in recognizing happy expressions. An analysis of response consistency showed that impaired recognition of fear could not be attributed simply to mistaking fear for another emotion. While it remains unclear why some subjects with amygdala damage included here are not impaired on our task, the results overall are consistent with the idea that the amygdala plays an important role in triggering knowledge related to threat and danger signaled by facial expressions. (C) 1999 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Adolphs1999a,
      author = {Adolphs, R and Tranel, D and Hamann, S and Young, AW and Calder, AJ and Phelps, EA and Anderson, A and Lee, GP and Damasio, AR},
      title = {Recognition of facial emotion in nine individuals with bilateral amygdala damage},
      journal = {NEUROPSYCHOLOGIA},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1999},
      volume = {37},
      number = {10},
      pages = {1111-1117}
    }
    
    AGGLETON, J. THE CONTRIBUTION OF THE AMYGDALA TO NORMAL AND ABNORMAL EMOTIONAL STATES {1993} TRENDS IN NEUROSCIENCES
    Vol. {16}({8}), pp. {328-333} 
    article  
    Abstract: Lesion studies in monkeys have provided some of the most compelling evidence for the involvement of the amygdala in emotional and social behaviour. In spite of this it has proved surprisingly difficult to uncover the precise nature of the role of the amygdala. A number of recent studies now indicate that the amygdala is involved in a specific class of stimulus-reward association and this discovery, combined with important anatomical findings, has made it possible to gain a much more detailed appreciation of the contribution of the amygdala to emotion in non-human primates. In parallel with this, it appears increasingly likely that amygdala dysfunction contributes to the emotional changes that accompany certain neurological disorders, including dementia and schizophrenia.
    BibTeX:
    @article{AGGLETON1993,
      author = {AGGLETON, JP},
      title = {THE CONTRIBUTION OF THE AMYGDALA TO NORMAL AND ABNORMAL EMOTIONAL STATES},
      journal = {TRENDS IN NEUROSCIENCES},
      publisher = {ELSEVIER SCI LTD},
      year = {1993},
      volume = {16},
      number = {8},
      pages = {328-333}
    }
    
    AGGLETON, J., BURTON, M. & PASSINGHAM, R. CORTICAL AND SUB-CORTICAL AFFERENTS TO THE AMYGDALA OF THE RHESUS-MONKEY (MACACA-MULATTA) {1980} BRAIN RESEARCH
    Vol. {190}({2}), pp. {347-368} 
    article  
    BibTeX:
    @article{AGGLETON1980,
      author = {AGGLETON, JP and BURTON, MJ and PASSINGHAM, RE},
      title = {CORTICAL AND SUB-CORTICAL AFFERENTS TO THE AMYGDALA OF THE RHESUS-MONKEY (MACACA-MULATTA)},
      journal = {BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1980},
      volume = {190},
      number = {2},
      pages = {347-368}
    }
    
    Aharon, I., Etcoff, N., Ariely, D., Chabris, C., O'Connor, E. & Breiter, H. Beautiful faces have variable reward value: fMRI and behavioral evidence {2001} NEURON
    Vol. {32}({3}), pp. {537-551} 
    article  
    Abstract: The brain circuitry processing rewarding and aversive stimuli is hypothesized to be at the core of motivated behavior. In this study, discrete categories of beautiful faces are shown to have differing reward values and to differentially activate reward circuitry in human subjects. In particular, young heterosexual males rate pictures of beautiful males and females as attractive, but exert effort via a keypress procedure only to view pictures of attractive females. Functional magnetic resonance imaging at 3 T shows that passive viewing of beautiful female faces activates reward circuitry, in particular the nucleus accumbens. An extended set of subcortical and paralimbic reward regions also appear to follow aspects of the keypress rather than the rating procedures, suggesting that reward circuitry function does not include aesthetic assessment.
    BibTeX:
    @article{Aharon2001,
      author = {Aharon, I and Etcoff, N and Ariely, D and Chabris, CF and O'Connor, E and Breiter, HC},
      title = {Beautiful faces have variable reward value: fMRI and behavioral evidence},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2001},
      volume = {32},
      number = {3},
      pages = {537-551}
    }
    
    ALBRIGHT, P. & BURNHAM, W. DEVELOPMENT OF A NEW PHARMACOLOGICAL SEIZURE MODEL - EFFECTS OF ANTICONVULSANTS ON CORTICAL-KINDLED AND AMYGDALA-KINDLED SEIZURES IN THE RAT {1980} EPILEPSIA
    Vol. {21}({6}), pp. {681-689} 
    article  
    BibTeX:
    @article{ALBRIGHT1980,
      author = {ALBRIGHT, PS and BURNHAM, WM},
      title = {DEVELOPMENT OF A NEW PHARMACOLOGICAL SEIZURE MODEL - EFFECTS OF ANTICONVULSANTS ON CORTICAL-KINDLED AND AMYGDALA-KINDLED SEIZURES IN THE RAT},
      journal = {EPILEPSIA},
      publisher = {LIPPINCOTT-RAVEN PUBL},
      year = {1980},
      volume = {21},
      number = {6},
      pages = {681-689}
    }
    
    Allison, T., Puce, A. & McCarthy, G. Social perception from visual cues: role of the STS region {2000} TRENDS IN COGNITIVE SCIENCES
    Vol. {4}({7}), pp. {267-278} 
    article  
    Abstract: Social perception refers to initial stages in the processing of information that culminates in the accurate analysis of the dispositions and intentions of other individuals. Single-cell recordings in monkeys, and neurophysiological and neuroimaging studies in humans, reveal that cerebral cortex in and near the superior temporal sulcus (STS) region is an important component of this perceptual system. In monkeys and humans, the STS region is activated by movements of the eyes, mouth, hands and body, suggesting that it is involved in analysis of biological motion. However, it is also activated by static images of the face and body, suggesting that it is sensitive to implied motion and more generally to stimuli that signal the actions of another individual. Subsequent analysis of socially relevant stimuli is carried out in the amygdala and orbitofrontal cortex, which supports a three-structure model proposed by brothers. The homology of human and monkey areas involved in social perception, and the functional interrelationships between the STS region and the ventral face area. are unresolved issues.
    BibTeX:
    @article{Allison2000,
      author = {Allison, T and Puce, A and McCarthy, G},
      title = {Social perception from visual cues: role of the STS region},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {2000},
      volume = {4},
      number = {7},
      pages = {267-278}
    }
    
    Anagnostaras, S., Gale, G. & Fanselow, M. Hippocampus and contextual fear conditioning: Recent controversies and advances {2001} HIPPOCAMPUS
    Vol. {11}({1}), pp. {8-17} 
    article  
    Abstract: Dorsal hippocampal (DH) lesions produce a severe deficit in recently, but not remotely, acquired contextual fear without impairing memory of discrete training stimuli, i.e., DH lesions produce an anterograde and time-limited retrograde amnesia specific to contextual memory. These data are consistent with the standard model which posits temporary involvement of the hippocampus in recent memory maintenance. However, three recent controversies apparently weaken the case for a selective mnemonic role for the hippocampus in contextual fear. First, although retrograde amnesia (from posttraining lesions) is severe, anterograde amnesia (from pretraining lesions) may be mild or nonexistent. Second, a performance, rather than mnemonic, account of contextual freezing deficits in hippocampal-lesioned animals has been offered. Third, damage to the entire hippocampus, including the ventral hippocampus, can produce a dramatic and temporally stable disruption of context and tone fear. These data are reviewed and explanations are offered as to why they do not necessarily challenge the standard model of hippocampal memory function in contextual fear. Finally, a more complete description of the hippocampus' proposed role in contextual fear is offered, along with new data supporting this view. In summary, the data support a specific mnemonic role for the DH in the acquisition and consolidation of contextual representations. (C) 2001 Wiley-Liss, Inc.
    BibTeX:
    @article{Anagnostaras2001,
      author = {Anagnostaras, SG and Gale, GD and Fanselow, MS},
      title = {Hippocampus and contextual fear conditioning: Recent controversies and advances},
      journal = {HIPPOCAMPUS},
      publisher = {WILEY-LISS},
      year = {2001},
      volume = {11},
      number = {1},
      pages = {8-17}
    }
    
    Anagnostaras, S., Maren, S. & Fanselow, M. Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: Within-subjects examination {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({3}), pp. {1106-1114} 
    article  
    Abstract: We have shown previously that electrolytic lesions of the dorsal hippocampus (DH) produce a severe deficit in contextual fear if made 1 d, but not 28 d, after fear conditioning (Kim and Fanselow, 1992). As such, the hippocampus seems to play a time-limited role in the consolidation of contextual fear conditioning. Here, we examine retrograde amnesia of contextual fear produced by DH lesions in a within-subjects design. Unlike our previous reports, rats had both a remote and recent memory at the time of the lesion. Rats were given 10 tone-shock pairings in one context (remote memory) and 10 tone-shock pairings in a distinct context (with a different tone) 50 d later (recent memory), followed by DH or sham lesions 1 d later. Relative to controls, DH-lesioned rats exhibited no deficit in remote contextual fear, but recent contextual fear memory was severely impaired. They also did not exhibit deficits in tone freezing. This highly specific deficit in recent contextual memory demonstrated in a within-subjects design favors mnemonic over performance accounts of hippocampal involvement in fear. These findings also provide further support for a time-limited role of the hippocampus in memory storage.
    BibTeX:
    @article{Anagnostaras1999,
      author = {Anagnostaras, SG and Maren, S and Fanselow, MS},
      title = {Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: Within-subjects examination},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {3},
      pages = {1106-1114}
    }
    
    Anderson, A., Christoff, K., Stappen, I., Panitz, D., Ghahremani, D., Glover, G., Gabrieli, J. & Sobel, N. Dissociated neural representations of intensity and valence in human olfaction {2003} NATURE NEUROSCIENCE
    Vol. {6}({2}), pp. {196-202} 
    article DOI  
    Abstract: Affective experience has been described in terms of two primary dimensions: intensity and valence. In the human brain, it is intrinsically difficult to dissociate the neural coding of these affective dimensions for visual and auditory stimuli, but such dissociation is more readily achieved in olfaction, where intensity and valence can be manipulated independently. Using event-related functional magnetic resonance imaging (fMRI), we found amygdala activation to be associated with intensity, and not valence, of odors. Activity in regions of orbitofrontal cortex, in contrast, were associated with valence independent of intensity. These findings show that distinct olfactory regions subserve the analysis of the degree and quality of olfactory stimulation, suggesting that the affective representations of intensity and valence draw upon dissociable neural substrates.
    BibTeX:
    @article{Anderson2003,
      author = {Anderson, AK and Christoff, K and Stappen, I and Panitz, D and Ghahremani, DG and Glover, G and Gabrieli, JDE and Sobel, N},
      title = {Dissociated neural representations of intensity and valence in human olfaction},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {2003},
      volume = {6},
      number = {2},
      pages = {196-202},
      doi = {{10.1038/nn1001}}
    }
    
    Anderson, A. & Phelps, E. Lesions of the human amygdala impair enhanced perception of emotionally salient events {2001} NATURE
    Vol. {411}({6835}), pp. {305-309} 
    article  
    Abstract: Commensurate with the importance of rapidly and efficiently evaluating motivationally significant stimuli, humans are probably endowed with distinct faculties(1,2) and maintain specialized neural structures to enhance their detection. Here we consider that a critical function of the human amygdala(3,4) is to enhance the perception of stimuli that have emotional significance. Under conditions of limited attention for normal perceptual awareness-that is, the attentional blink(5,6)-we show that healthy observers demonstrate robust benefits for the perception of verbal stimuli of aversive content compared with stimuli of neutral content. In contrast, a patient with bilateral amygdala damage has no enhanced perception for such aversive stimulus events. Examination of patients with either left or right amygdala resections shows that the enhanced perception of aversive words depends specifically on the left amygdala. All patients comprehend normally the affective meaning of the stimulus events, despite the lack of evidence for enhanced perceptual encoding of these events in patients with left amygdala lesions. Our results reveal a neural substrate for affective influences on perception, indicating that similar neural mechanisms may underlie the affective modulation of both recollective(7-9) and perceptual experience.
    BibTeX:
    @article{Anderson2001,
      author = {Anderson, AK and Phelps, EA},
      title = {Lesions of the human amygdala impair enhanced perception of emotionally salient events},
      journal = {NATURE},
      publisher = {MACMILLAN PUBLISHERS LTD},
      year = {2001},
      volume = {411},
      number = {6835},
      pages = {305-309}
    }
    
    Anwyl, R. Metabotropic glutamate receptors: electrophysiological properties and role in plasticity {1999} BRAIN RESEARCH REVIEWS
    Vol. {29}({1}), pp. {83-120} 
    article  
    Abstract: Electrophysiological research on mGluRs is now very extensive, and it is clear that activation of mGluRs results in a large number of diverse cellular actions. Studies of mGluRs and on ionic channels has clearly demonstrated that mGluR activation has a widespread and potent inhibitory action on both voltage-gated Ca2+ channels and K+ channels. Inhibition of N-type Ca2+ channels, and inhibition of Ca++-dependent K+ current, I-AHP, and I-M being particularly prominent. Potentiation of activation of both Ca2+ and K+ channels has also been observed, although less prominently than inhibition, but mGluR-mediated activation of non-selective cationic channels is widespread. In a small number of studies, generation of an mGluR-mediated slow excitatory postsynaptic potential has been demonstrated as a consequence of the effect of mGluR activation on ion channels, such as activation of a non-selective cationic channels. Although certain mGluR-modulation of channels is a consequence of direct G-protein-linked action, for example, inhibition of Ca2+ channels, many other effects occur as a result of activation of intracellular messenger pathways, but at present, little progress has been made on the identification of the messengers. The field of study of the involvement of mGluRs in synaptic plasticity is very large. Evidence for the involvement of mGluRs in one form of LTD induction in the cerebellum and hippocampus is now particularly impressive. However, the role of mGluRs in LTP induction continues to be a source of dispute, and resolution of the question of the exact involvement of mGluRs in the induction of LTP will have to await the production of more selective ligands and of selective gene knockouts. (C) 1999 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Anwyl1999,
      author = {Anwyl, R},
      title = {Metabotropic glutamate receptors: electrophysiological properties and role in plasticity},
      journal = {BRAIN RESEARCH REVIEWS},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1999},
      volume = {29},
      number = {1},
      pages = {83-120}
    }
    
    ARRIAGADA, P., GROWDON, J., HEDLEYWHYTE, E. & HYMAN, B. NEUROFIBRILLARY TANGLES BUT NOT SENILE PLAQUES PARALLEL DURATION AND SEVERITY OF ALZHEIMERS-DISEASE {1992} NEUROLOGY
    Vol. {42}({3}), pp. {631-639} 
    article  
    Abstract: We studied the accumulation of neurofibrillary tangles (NFTs) and senile plaques (SPs) in 10 Alzheimer's disease patients who had been examined during life. We counted NFTs and SPs in 13 cytoarchitectural regions representing limbic, primary sensory, and association cortices, and in subcortical neurotransmitter-specific areas. The degree of neuropathologic change was compared with the severity of dementia, as assessed by the Blessed Dementia Scale and duration of illness. We found that (1) the severity of dementia was positively related to the number of NFTs in neocortex, but not to the degree of SP deposition; (2) NFTs accumulate in a consistent pattern reflecting hierarchic vulnerability of individual cytoarchitectural fields; (3) NFTs appeared in the entorhinal cortex, CA1/subiculum field of the hippocampal formation, and the amygdala early in the disease process; and (4) the degree of SP deposition was also related to a hierarchic vulnerability of certain brain areas to accumulate SPs, but the pattern of SP distribution was different from that of NFT.
    BibTeX:
    @article{ARRIAGADA1992,
      author = {ARRIAGADA, PV and GROWDON, JH and HEDLEYWHYTE, ET and HYMAN, BT},
      title = {NEUROFIBRILLARY TANGLES BUT NOT SENILE PLAQUES PARALLEL DURATION AND SEVERITY OF ALZHEIMERS-DISEASE},
      journal = {NEUROLOGY},
      publisher = {LIPPINCOTT-RAVEN PUBL},
      year = {1992},
      volume = {42},
      number = {3},
      pages = {631-639},
      note = {43RD ANNUAL MEETING OF THE AMERICAN ACADEMY OF NEUROLOGY, BOSTON, MA, APR, 1991}
    }
    
    Bale, T., Contarino, A., Smith, G., Chan, R., Gold, L., Sawchenko, P., Koob, G., Vale, W. & Lee, K. Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress {2000} NATURE GENETICS
    Vol. {24}({4}), pp. {410-414} 
    article  
    Abstract: Corticotropin-releasing hormone (Crh) is a critical coordinator of the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, Crh released from the paraventricular nucleus (PVN) of the hypothalamus activates Crh receptors on anterior pituitary corticotropes, resulting in release of adrenocorticotropic hormone (Acth) into the bloodstream. Acth in turn activates Acth receptors in the adrenal cortex to increase synthesis and release of glucocorticoids(1). The receptors for Crh, Crhr1 and Crhr2, are found throughout the central nervous system and periphery. Crh has a higher affinity for Crhr1 than for Crhr2, and urocortin (Ucn); a Crh-related peptide, is thought to be the endogenous ligand for Crhr2 because it binds with almost 40-fold higher affinity than does Crh (ref. 2). Crhr1 and Crhr2 share approximately 71% amino acid sequence similarity and are distinct in their localization within the brain and peripheral tissues(3-6). We generated mice deficient for Crhr2 to determine the physiological role of this receptor. Crhr2-mutant mice are hypersensitive to stress and display increased anxiety-like behaviour. Mutant mice have normal basal feeding and weight gain, but decreased food intake following food deprivation. intravenous Ucn produces no effect on mean arterial pressure in the mutant mice.
    BibTeX:
    @article{Bale2000,
      author = {Bale, TL and Contarino, AB and Smith, GW and Chan, R and Gold, LH and Sawchenko, PE and Koob, GF and Vale, WW and Lee, KF},
      title = {Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress},
      journal = {NATURE GENETICS},
      publisher = {NATURE AMERICA INC},
      year = {2000},
      volume = {24},
      number = {4},
      pages = {410-414}
    }
    
    Bannerman, D., Rawlins, J., McHugh, S., Deacon, R., Yee, B., Bast, T., Zhang, W., Pothuizen, H. & Feldon, J. Regional dissociations within the hippocampus - memory and anxiety {2004} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {28}({3}), pp. {273-283} 
    article DOI  
    Abstract: The amnestic effects of hippocampal lesions are well documented, leading to numerous memory-based theories of hippocampal function. It is debatable, however, whether any one of these theories can satisfactorily account for all the consequences of hippocampal damage: Hippocampal lesions also result in behavioural disinhibition and reduced anxiety. A growing number of studies now suggest that these diverse behavioural effects may be associated with different hippocampal subregions. There is evidence for at least two distinct functional domains, although recent neuroanatomical studies suggest this may be an underestimate. Selective lesion studies show that the hippocampus is functionally subdivided along the septotemporal axis into dorsal and ventral regions, each associated with a distinct set of behaviours. Dorsal hippocampus has a preferential role in certain forms of learning and memory, notably spatial learning, but ventral hippocampus may have a preferential role in brain processes associated with anxiety-related behaviours. The latter's role in emotional processing is also distinct from that of the amygdala, which is associated specifically with fear. Gray and McNaughton's theory can in principle incorporate these apparently distinct hippocampal functions, and provides a plausible unitary account for the multiple facets of hippocampal function. (C) 2004 Elsevier Ltd. All rights reserved.
    BibTeX:
    @article{Bannerman2004,
      author = {Bannerman, DM and Rawlins, JNP and McHugh, SB and Deacon, RMJ and Yee, BK and Bast, T and Zhang, WN and Pothuizen, HHJ and Feldon, J},
      title = {Regional dissociations within the hippocampus - memory and anxiety},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2004},
      volume = {28},
      number = {3},
      pages = {273-283},
      doi = {{10.1016/j.neubiorev.2004.03.004}}
    }
    
    Bardo, M. Neuropharmacological mechanisms of drug reward: Beyond dopamine in the nucleus accumbens {1998} CRITICAL REVIEWS IN NEUROBIOLOGY
    Vol. {12}({1-2}), pp. {37-67} 
    article  
    Abstract: Multiple lines of research have implicated the mesolimbic dopamine system in drug reward measured by either the drug self-administration or conditioned place preference paradigm. The present review summarizes recent work that examines the neuropharmacological mechanisms by which drugs impinge on this dopaminergic neural circuitry, as well as other systems that provide input and output circuits to the mesolimbic dopamine system. Studies examining the effect of selective agonist and antagonist drugs administered systemically have indicated that multiple neurotransmitters are involved, including dopamine, serotonin, acetylcholine, glutamate, GABA, and various peptides. Direct microinjection studies have also provided crucial evidence indicating that, in addition to the mesolimbic dopamine system, other structures play a role in drug reward, including the ventral pallidum, amygdala, hippocampus, hypothalamus, and pedunculopontine tegmental nucleus. GABAergic circuitry descending from the nucleus accumbens io the pedunculopontine tegmental nucleus via the ventral pallidum appears to be especially important in directing the behavioral sequelae associated with reward produced by various drugs of abuse. However, activation of the reward circuitry is achieved differently for various drugs of abuse. With amphetamine and cocaine, initiation of reward is controlled within the nucleus accumbens and prefrontal cortex, respectively. With opiates, initiation of reward involves the ventral tegmental area, nucleus accumbens, hippocampus, and hypothalamus. It is not clear presently if these multiple anatomical structures mediate opiate reward by converging on a single output system or multiple output systems.
    BibTeX:
    @article{Bardo1998,
      author = {Bardo, MT},
      title = {Neuropharmacological mechanisms of drug reward: Beyond dopamine in the nucleus accumbens},
      journal = {CRITICAL REVIEWS IN NEUROBIOLOGY},
      publisher = {BEGELL HOUSE INC},
      year = {1998},
      volume = {12},
      number = {1-2},
      pages = {37-67}
    }
    
    Baron-Cohen, S., Ring, H., Bullmore, E., Wheelwright, S., Ashwin, C. & Williams, S. The amygdala theory of autism {2000} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {24}({3}), pp. {355-364} 
    article  
    Abstract: Brothers (Brothers L. Concepts in Neuroscience 1990;1:27-51) proposed a network of neural regions that comprise the ``social brain'', which includes the amygdala. Since the childhood psychiatric condition of autism involves deficits in ``social intelligence'', it is plausible that autism may be caused by an amygdala abnormality. In this paper we review the evidence for a social function of the amygdala. This includes reference to the Kluver-Bucy syndrome (which Hetzler and Griffin suggested may serve as an animal model of autism). We then review evidence for an amygdala deficit in people with autism, who are well known to have deficits in social behaviour. This includes a detailed summary of our recent functional magnetic resonance imaging (fMRI) study involving judging from the expressions of another person's eyes what that other person might be thinking or feeling. In this study, patients with autism or AS did not activate the amygdala when making mentalistic inferences from the eyes, whilst people without autism did show amygdala activity. The amygdala is therefore proposed to be one of several neural regions that are abnormal in autism. We conclude that the amygdala theory of autism contains promise and suggest some new lines of research. (C) 2000 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Baron-Cohen2000,
      author = {Baron-Cohen, S and Ring, HA and Bullmore, ET and Wheelwright, S and Ashwin, C and Williams, SCR},
      title = {The amygdala theory of autism},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2000},
      volume = {24},
      number = {3},
      pages = {355-364}
    }
    
    Baron-Cohen, S., Ring, H., Wheelwright, S., Bullmore, E., Brammer, M., Simmons, A. & Williams, S. Social intelligence in the normal and autistic brain: an fMRI study {1999} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {11}({6}), pp. {1891-1898} 
    article  
    Abstract: There is increasing support for the existence of `social intelligence' [Humphrey (1984) Consciousness Regained], independent of general intelligence. Brothers [(1990) J. Cog. Neurosci., 4, 107-118] proposed a network of neural regions that comprise the `social brain': the orbito-frontal cortex (OFC), superior temporal gyrus (STG) and amygdala. We tested Brothers' theory by examining both normal subjects as well as patients with high-functioning autism or Asperger syndrome (AS), who are well known to have deficits in social intelligence, and perhaps deficits in amygdala function [Bauman & Kemper (1988) J, Neuropath. Exp. Neurol,, 47, 369], We used a test of judging from the expressions of another person's eyes what that other person might be thinking or feeling. Using functional magnetic resonance imaging (fMRI) we confirmed Brothers' prediction that the STG and amygdala show increased activation when using social intelligence. Some areas of the prefrontal cortex also showed activation. In contrast, patients with autism or AS activated the fronto-temporal regions but not the amygdala when making mentalistic inferences from the eyes. These results provide support for the social brain theory of normal function, and the amygdala theory of autism.
    BibTeX:
    @article{Baron-Cohen1999,
      author = {Baron-Cohen, S and Ring, HA and Wheelwright, S and Bullmore, ET and Brammer, MJ and Simmons, A and Williams, SCR},
      title = {Social intelligence in the normal and autistic brain: an fMRI study},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      publisher = {BLACKWELL SCIENCE LTD},
      year = {1999},
      volume = {11},
      number = {6},
      pages = {1891-1898}
    }
    
    Bartels, A. & Zeki, S. The neural correlates of maternal and romantic love {2004} NEUROIMAGE
    Vol. {21}({3}), pp. {1155-1166} 
    article DOI  
    Abstract: Romantic and maternal love are highly rewarding experiences. Both are linked to the perpetuation of the species and therefore have a closely linked biological function of crucial evolutionary importance. Yet almost nothing is known about their neural correlates in the human. We therefore used fMRI to measure brain activity in mothers while they viewed pictures of their own and of acquainted children, and of their best friend and of acquainted adults as additional controls. The activity specific to maternal attachment was compared to that associated to romantic love described in our earlier study and to the distribution of attachment-mediating neurohormones established by other studies. Both types of attachment activated regions specific to each, as well as overlapping regions in the brain's reward system that coincide with areas rich in oxytocin and vasopressin receptors. Both deactivated a common set of regions associated with negative emotions, social judgment and `mentalizing', that is, the assessment of other people's intentions and emotions. We conclude that human attachment employs a push-pull mechanism that overcomes social distance by deactivating networks used for critical social assessment and negative emotions, while it bonds individuals through the involvement of the reward circuitry, explaining the power of love to motivate and exhilarate. (C) 2004 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Bartels2004,
      author = {Bartels, A and Zeki, S},
      title = {The neural correlates of maternal and romantic love},
      journal = {NEUROIMAGE},
      publisher = {ACADEMIC PRESS INC ELSEVIER SCIENCE},
      year = {2004},
      volume = {21},
      number = {3},
      pages = {1155-1166},
      doi = {{10.1016/j.neuroimage.2003.11.003}}
    }
    
    BAUM, M. & EVERITT, B. INCREASED EXPRESSION OF C-FOS IN THE MEDIAL PREOPTIC AREA AFTER MATING IN MALE-RATS - ROLE OF AFFERENT INPUTS FROM THE MEDIAL AMYGDALA AND MIDBRAIN CENTRAL TEGMENTAL FIELD {1992} NEUROSCIENCE
    Vol. {50}({3}), pp. {627-646} 
    article  
    Abstract: Immunocytochemical methods were used to localize the protein product of the immediate-early gene, c-fos, in male rats after exposure to, or direct physical interaction with, oestrous females. Increasing amounts of physical contact with a female, with resultant olfactory-vomeronasal and/or genital-somatosensory inputs, caused corresponding increments in c-fos expression in the medial preoptic area, the caudal part of the bed nucleus of the stria terminalis, the medial amygdala, and the midbrain central tegmental field. Males bearing unilateral electrothermal lesions of the olfactory peduncle showed a significant reduction in c-fos expression in the ipsilateral medial amygdala, but not in other structures, provided their coital interaction with oestrous females was restricted to mount-thrust and occasional intromissive patterns due to repeated application of lidocaine anaesthetic to the penis. No such lateralization of c-fos expression occurred in other males with unilateral olfactory lesions which were allowed to intromit and ejaculate with a female. These results suggest that olfactory inputs, possibly of vomeronasal origin, contribute to the activation of c-fos in the medial amygdala. However, lesion-induced deficits in this type of afferent input to the nervous system appear to be readily compensated for by the genital somatosensory input derived from repeated intromissions. Unilateral excitotoxic lesions of the medial preoptic area, made by infusing quinolinic acid, failed to reduce c-fos expression in the ipsilateral or contralateral medial amygdala or central tegmental field following ejaculation. By contrast, combined, unilateral excitotoxic lesions of the medial amygdala and the central tegmental field significantly reduced c-fos expression in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area after mating; no such assymetry in c-fos expression occurred when lesions were restricted to either the medial amygdala or central tegmental field. This suggests that afferent inputs from the central tegmental field (probably of genital-somatosensory origin) and from the medial amygdala (probably of olfactory-vomeronasal origin) interact to promote cellular activity, and the resultant induction of c-fos, in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area. The monitoring of neuronal c-fos expression provides an effective means of studying the role of sensory factors in governing the activity of integrated neural structures which control the expression of a complex social behaviour.
    BibTeX:
    @article{BAUM1992,
      author = {BAUM, MJ and EVERITT, BJ},
      title = {INCREASED EXPRESSION OF C-FOS IN THE MEDIAL PREOPTIC AREA AFTER MATING IN MALE-RATS - ROLE OF AFFERENT INPUTS FROM THE MEDIAL AMYGDALA AND MIDBRAIN CENTRAL TEGMENTAL FIELD},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1992},
      volume = {50},
      number = {3},
      pages = {627-646}
    }
    
    Baxter, M. & Murray, E. The amygdala and reward {2002} NATURE REVIEWS NEUROSCIENCE
    Vol. {3}({7}), pp. {563-573} 
    article DOI  
    Abstract: The amygdala - an almond-shaped group of nuclei at the heart of the telencephalon has been associated with a range of cognitive functions, including emotion, learning, memory, attention and perception. Most current views of amygdala function emphasize its role in negative emotions, such as fear, and in linking negative emotions with other aspects of cognition, such as learning and memory. However, recent evidence supports a role for the amygdala in processing positive emotions as well as negative ones, including learning about the beneficial biological value of stimuli. Indeed, the amygdala's role in stimulus-reward learning might be just as important as its role in processing negative affect and fear conditioning.
    BibTeX:
    @article{Baxter2002,
      author = {Baxter, MG and Murray, EA},
      title = {The amygdala and reward},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2002},
      volume = {3},
      number = {7},
      pages = {563-573},
      doi = {{10.1038/nrn875}}
    }
    
    Baxter, M., Parker, A., Lindner, C., Izquierdo, A. & Murray, E. Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({11}), pp. {4311-4319} 
    article  
    Abstract: Goal-directed actions are guided by expected outcomes of those actions. Humans with bilateral damage to ventromedial prefrontal cortex, or the amygdala, are deficient in their ability to use information about positive and negative outcomes to guide their choice behavior. Similarly, rats and monkeys with orbital prefrontal or amygdala damage have been found to be impaired in their responses to changing values of outcomes. In the present study, we tested whether direct, functional interaction between the amygdala and the orbital prefrontal cortex is necessary for guiding behavior based on expected outcomes. Unlike control monkeys, rhesus monkeys with surgical disconnection of these two structures, achieved by crossed unilateral lesions of the amygdala in one hemisphere and orbital prefrontal cortex in the other, combined with forebrain commissurotomy, were unable to adjust their choice behavior after a change in the outcome (here, a reduction in the value of a particular reinforcer). The lesions did not affect motivation to work for a food reinforcer, or food preferences, per se. Hence, the amygdala and orbital prefrontal cortex act as part of an integrated neural system guiding decision-making and adaptive response selection.
    BibTeX:
    @article{Baxter2000,
      author = {Baxter, MG and Parker, A and Lindner, CCC and Izquierdo, AD and Murray, EA},
      title = {Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {11},
      pages = {4311-4319}
    }
    
    Bechara, A. & Damasio, H. Decision-making and addiction (part I): impaired activation of somatic states in substance dependent individuals when pondering decisions with negative future consequences {2002} NEUROPSYCHOLOGIA
    Vol. {40}({10}), pp. {1675-1689} 
    article  
    Abstract: Some substance dependent individuals (SDI) suffer from a decision-making impairment akin to that seen in neurological patients with lesions of the ventromedial (VM) prefrontal cortex. The somatic-marker hypothesis posits that decision-making is a process that depends on emotion and that deficits in emotional signaling will lead to poor decision-making. In this study, we tested the hypothesis that SDI who perform disadvantageously on a decision-making instrument, the gambling task (GT), have a deficit in the somatic signals that help guide their decision in the advantageous direction. Since deficits in decision-making/somatic markers can also result from dysfunctional amygdala, we asked indirectly (i.e. via tests sensitive to VM or amygdala dysfunction) whether such a deficit in SDI is restricted to VM dysfunction or includes the amygdala. Using the GT, and skin conductance response (SCR) as an index of somatic state activation, we studied groups of SDI (n = 46), normal controls (n = 49), and VM patients (n = 10). A subgroup of SDI showed defective performance on the GT coupled with impaired anticipatory SCR, but normal SCR to punishment, and normal acquisition of conditioned SCR to an aversive loud sound. This supports the hypothesis that the poor decision-making in some SDI is associated with defective somatic state activation that is linked to a dysfunctional VM cortex. Thus, the dysfunctional VM cortex underlying the ``myopia'' for the future in some SDI may be one of the principle mechanisms underlying the transition from casual substance taking to compulsive and uncontrollable behavior. (C) 2002 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Bechara2002,
      author = {Bechara, A and Damasio, H},
      title = {Decision-making and addiction (part I): impaired activation of somatic states in substance dependent individuals when pondering decisions with negative future consequences},
      journal = {NEUROPSYCHOLOGIA},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2002},
      volume = {40},
      number = {10},
      pages = {1675-1689}
    }
    
    Bechara, A., Damasio, H. & Damasio, A. Emotion, decision making and the orbitofrontal cortex {2000} CEREBRAL CORTEX
    Vol. {10}({3}), pp. {295-307} 
    article  
    Abstract: The somatic marker hypothesis provides a systems-level neuroanatomical and cognitive framework for decision making and the influence on it by emotion. The key idea of this hypothesis is that decision making is a process that is influenced by marker signals that arise in bioregulatory processes, including those that express themselves in emotions and feelings. This influence can occur at multiple levels of operation, some of which occur consciously and some of which occur non-consciously. Here we review studies that confirm various predictions from the hypothesis. The orbitofrontal cortex represents one critical structure in a neural system subserving decision making. Decision making is not mediated by the orbitofrontal cortex alone, hut arises from large-scale systems that include other cortical and subcortical components. Such structures include the amygdala, the somatosensory/insular cortices and the peripheral nervous system. Here we focus only on the role of the orbitofrontal cortex in decision making and emotional processing, and the relationship between emotion, decision making and other cognitive functions of the frontal lobe. namely working memory.
    BibTeX:
    @article{Bechara2000,
      author = {Bechara, A and Damasio, H and Damasio, AR},
      title = {Emotion, decision making and the orbitofrontal cortex},
      journal = {CEREBRAL CORTEX},
      publisher = {OXFORD UNIV PRESS INC},
      year = {2000},
      volume = {10},
      number = {3},
      pages = {295-307}
    }
    
    Bechara, A., Damasio, H., Damasio, A. & Lee, G. Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({13}), pp. {5473-5481} 
    article  
    Abstract: The somatic marker hypothesis proposes that decision-making is a process that depends on emotion. Studies have shown that damage of the ventromedial prefrontal (VMF) cortex precludes the ability to use somatic (emotional) signals that are necessary for guiding decisions in the advantageous direction. However, given the role of the amygdala in emotional processing, we asked whether amygdala damage also would interfere with decision-making. Furthermore, we asked whether there might be a difference between the roles that the amygdala and VMF cortex play in decision-making. To address these two questions, we studied a group of patients with bilateral amygdala, but not VMF, damage and a group of patients with bilateral VMF, but not amygdala, damage. We used the ``gambling task'' to measure decision-making performance and electrodermal activity (skin conductance responses, SCR) as an index of somatic state activation. All patients, those with amygdala damage as well as those with VMF damage, were (1) impaired on the gambling task and (2) unable to develop anticipatory SCRs while they pondered risky choices. However, VMF patients were able to generate SCRs when they received a reward or a punishment (play money), whereas amygdala patients failed to do so. in a Pavlovian conditioning experiment the VMF patients acquired a conditioned SCR to visual stimuli paired with an aversive loud sound, whereas amygdala patients failed to do so. The results suggest that amygdala damage is associated with impairment in decision-making and that the roles played by the amygdala and VMF in decision-making are different.
    BibTeX:
    @article{Bechara1999,
      author = {Bechara, A and Damasio, H and Damasio, AR and Lee, GP},
      title = {Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {13},
      pages = {5473-5481}
    }
    
    Bechara, A., Dolan, S., Denburg, N., Hindes, A., Anderson, S. & Nathan, P. Decision-malting deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers {2001} NEUROPSYCHOLOGIA
    Vol. {39}({4}), pp. {376-389} 
    article  
    Abstract: A decision-making instrument known as the `gambling task' was used, which has been shown to be sensitive to the decision-making impairment of patients with bilateral lesions of the ventromedial prefrontal cortex (VM). Three groups of subjects were tested, substance dependent individuals (SD) (n = 41), normal controls (n = 40), and VM patients (n = 5). All SD met the DSM-IV criteria for dependence, with either alcohol or stimulants (metamphetamine or cocaine) as the primary substance of choice. The results revealed a significant impairment in the performance of SD relative to normal controls. A significantly high proportion of SD (61 vs. only 32.5% of normal controls) performed within the range of the VM patients, while the rest performed within the range of normal controls. General demographic Factors such as age, sex, and level of education could not explain these differences in performance. As well, differences in performance were not explained by intelligence (IQ), memory, or performance on standard executive function/frontal lobe tests. Performance on the gambling task was best predicted by a combination of factors; including duration of abstinence, years of abuse, relapses and limes in treatment, and the ability to hold gainful employment. The results support the hypothesis that impairment in decision-making linked to a dysfunctional VM cortex is associated with at least a sub-group of SD. (C) 2001 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Bechara2001,
      author = {Bechara, A and Dolan, S and Denburg, N and Hindes, A and Anderson, SW and Nathan, PE},
      title = {Decision-malting deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers},
      journal = {NEUROPSYCHOLOGIA},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2001},
      volume = {39},
      number = {4},
      pages = {376-389},
      note = {29th Annual Meeting of the Society-for-Neuroscience, MIAMI BEACH, FLORIDA, OCT 23-28, 1999}
    }
    
    BECHARA, A., TRANEL, D., DAMASIO, H., ADOLPHS, R., ROCKLAND, C. & DAMASIO, A. DOUBLE DISSOCIATION OF CONDITIONING AND DECLARATIVE KNOWLEDGE RELATIVE TO THE AMYGDALA AND HIPPOCAMPUS IN HUMANS {1995} SCIENCE
    Vol. {269}({5227}), pp. {1115-1118} 
    article  
    Abstract: A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning. Finally, a patient with bilateral damage to both amygdala and hippocampal formation acquired neither the conditioning nor the facts. These findings demonstrate a double dissociation of conditioning and declarative knowledge relative to the human amygdala and hippocampus.
    BibTeX:
    @article{BECHARA1995,
      author = {BECHARA, A and TRANEL, D and DAMASIO, H and ADOLPHS, R and ROCKLAND, C and DAMASIO, AR},
      title = {DOUBLE DISSOCIATION OF CONDITIONING AND DECLARATIVE KNOWLEDGE RELATIVE TO THE AMYGDALA AND HIPPOCAMPUS IN HUMANS},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVAN SCIENCE},
      year = {1995},
      volume = {269},
      number = {5227},
      pages = {1115-1118}
    }
    
    BECK, C. & FIBIGER, H. CONDITIONED FEAR-INDUCED CHANGES IN BEHAVIOR AND IN THE EXPRESSION OF THE IMMEDIATE-EARLY GENE C-FOS - WITH AND WITHOUT DIAZEPAM PRETREATMENT {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({1, Part 2}), pp. {709-720} 
    article  
    Abstract: The synthesis of Fos, the protein product of the immediate early gene c-fos, was used to map metabolically some of the neural substrates of conditioned fear in the rat. analysis of the behaviors emitted by the rats during the test session provided strong evidence that the conditioning procedure was effective. Exposure to the environment in which they had previously received footshock significantly increased the number of Fos-like immunoreactive neurons in nearly 50 brain regions, both cortical and subcortical. Among the structures showing the most dramatic increases in fear-induced c-fos expression were the cingulate, piriform, infralimbic, and retrosplenial cortices, the anterior olfactory nucleus, claustrum, endopiriform nucleus, nucleus accumbens shell, lateral septal nucleus, various amygdalar nuclei, paraventricular thalamic nucleus, ventral lateral geniculate nucleus, the ventromedial, lateral, and dorsal hypothalamic nuclei, the ventral tegmental area, and the supramammillary area. These data demonstrate that a relatively simple classical conditioning procedure activates a large number of widely dispersed cortical and subcortical structures. Some of the structures showing increased c-fos expression have important autonomic functions and may therefore have reflected centrally mediated changes in blood pressure and respiration produced by the anxiogenic stimuli. In a second experiment, the effects of pretreatment with the anxiolytic drug diazepam (2.5, 5.0, or 10 mg/kg) were evaluated. The benzodiazepine produced dose-related decreases in the frequency of crouching (freezing) elicited by the aversively conditioned contextual cues. Diazepam also produced dose-related decreases in conditioned stress-induced c-fos expression in all but one structure, the effects being statistically significant in 38 of 60 sampled structures. Diazepam dose dependently increased fear-induced c-fos expression in the central nucleus of the amygdala. There was considerable regional variability with respect to sensitivity to diazepam, the retrosplenial cortex and the supramammillary area being the only two structures to show decreases after the lowest dose of diazepam. In contrast, the entorhinal cortex, nucleus accumbens core, ventromedial and posterior hypothalamic nuclei, median raphe, and locus coeruleus were particularly resistant to diazepam, all failing to show statistically significant decreases in conditioned fear-induced c-fos expression even at the highest dose. The extent to which diazepam decreased conditioned stress-induced c-fos expression was unrelated to previous estimates of benzodiazepine receptor density in the sampled structures.
    BibTeX:
    @article{BECK1995,
      author = {BECK, CHM and FIBIGER, HC},
      title = {CONDITIONED FEAR-INDUCED CHANGES IN BEHAVIOR AND IN THE EXPRESSION OF THE IMMEDIATE-EARLY GENE C-FOS - WITH AND WITHOUT DIAZEPAM PRETREATMENT},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1995},
      volume = {15},
      number = {1, Part 2},
      pages = {709-720}
    }
    
    BEHBEHANI, M. FUNCTIONAL-CHARACTERISTICS OF THE MIDBRAIN PERIAQUEDUCTAL GRAY {1995} PROGRESS IN NEUROBIOLOGY
    Vol. {46}({6}), pp. {575-605} 
    article  
    Abstract: The major functions of the midbrain periaqueductal gray (PAG), including pain and analgesia, fear and anxiety, vocalization, lordosis and cardiovascular control are considered in this review article. The PAG is an important site in ascending pain transmission. It receives afferents from nociceptive neurons in the spinal cord and sends projections to thalamic nuclei that process nociception. The PAG is also a major component of a descending pain inhibitory system. Activation of this system inhibits nociceptive neurons in the dorsal horn of the sinal cord. The dorsal PAG is a major site for processing of fear and anxiety. It interacts with the amygdala and its lesion alters fear and anxiety produced by stimulation of amygdala. Stimulation of PAG produces vocalization and its lesion produces mutism. The firing of many cells within the FAG correlates with vocalization. The PAG is a major site for lordosis and this role of PAG is mediated by a pathway connecting the medial preoptic with the PAG. The cardiovascular controlling network within the PAG are organized in columns. The dorsal column is involved in presser and the ventrolateral column mediates depressor responses. The major intrinsic circuit within the PAG is a tonically-active GABAergic network and inhibition of this network is an important mechanism for activation of outputs of the PAG. The various functions of the PAG are interrelated and there is a significant interaction between different functional components of the PAG. Using the curent information about the anatomy, physiology, and pharmacology of the PAG, a model is proposed to account for the interactions between these different functional components.
    BibTeX:
    @article{BEHBEHANI1995,
      author = {BEHBEHANI, MM},
      title = {FUNCTIONAL-CHARACTERISTICS OF THE MIDBRAIN PERIAQUEDUCTAL GRAY},
      journal = {PROGRESS IN NEUROBIOLOGY},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1995},
      volume = {46},
      number = {6},
      pages = {575-605}
    }
    
    Bejjani, B., Damier, P., Arnulf, I., Thivard, L., Bonnet, A., Dormont, D., Cornu, P., Pidoux, B., Samson, Y. & Agid, Y. Transient acute depression induced by high-frequency deep-brain stimulation {1999} NEW ENGLAND JOURNAL OF MEDICINE
    Vol. {340}({19}), pp. {1476-1480} 
    article  
    BibTeX:
    @article{Bejjani1999,
      author = {Bejjani, BP and Damier, P and Arnulf, I and Thivard, L and Bonnet, AM and Dormont, D and Cornu, P and Pidoux, B and Samson, Y and Agid, Y},
      title = {Transient acute depression induced by high-frequency deep-brain stimulation},
      journal = {NEW ENGLAND JOURNAL OF MEDICINE},
      publisher = {MASSACHUSETTS MEDICAL SOC},
      year = {1999},
      volume = {340},
      number = {19},
      pages = {1476-1480}
    }
    
    Benes, F. & Berretta, S. GABAergic interneurons: Implications for understanding schizophrenia and bipolar disorder {2001} NEUROPSYCHOPHARMACOLOGY
    Vol. {25}({1}), pp. {1-27} 
    article  
    Abstract: A core component to corticolimbic circuitry is the GABAergic interneuron. Neuroanatomic studies conducted over the past century have demonstrated several subtypes of interneuron defined by characteristic morphological appearances in Golgi-stained preparations, More recently, both cytochemical and electrophysiological techniques have defined various subtypes of GABA neuron according to synaptic connections, electrophysiological properties and neuropeptide content. These cells provide both inhibitory and disinhibitory modulation of cortical and hippocampal circuits and contribute to the generation of oscillatory rhythms, discriminative information processing and gating of sensory information within the corticolimbic system. All of these functions are abnormal in schizophrenia. Recent postmortem studies have provided consistent evidence that a defect of GABAergic neurotransmission probably plays a role in both schizophrenia and bipolar disorder. Many now believe that such a disturbance may be related to a perturbation of early development, one that may result in a disturbance of cell migration and the formation of normal lamination The ingrowth of extrinsic afferents, such as the mesocortical dopamine projections, may ``trigger'' the appearance of a defective GABA system, particularly under stressful conditions when the modulation of the dopamine system is likely to be altered. Based on the regional and subregional distribution of changes in GABA cells in schizophrenia and bipolar disorder, it has been postulated that the basolateral nucleus oft he amygdala may contribute to these abnormalities through an increased flow of excitatory activity. By using ``partial'' modeling, changes in the GABA system remarkably similar to those seen in schizophrenia and bipolar disorder have been induced in mt hippocampus. In the years to come, continued investigations of the GABA system in rodent, primate and human brain and the characterization of changes in specific phenotypic subclasses of interneurons in schizophrenia and bipolar disorder will undoubtedly provide important new insights into how the integration of this transmitter system may be altered in neuropsychiatric disease. [Neuropsychopharmacology 25:1-27, 2001] (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
    BibTeX:
    @article{Benes2001,
      author = {Benes, FM and Berretta, S},
      title = {GABAergic interneurons: Implications for understanding schizophrenia and bipolar disorder},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2001},
      volume = {25},
      number = {1},
      pages = {1-27}
    }
    
    BERGERSWEENEY, J., HECKERS, S., MESULAM, M., WILEY, R., LAPPI, D. & SHARMA, M. DIFFERENTIAL-EFFECTS ON SPATIAL NAVIGATION OF IMMUNOTOXIN-INDUCED CHOLINERGIC LESIONS OF THE MEDIAL SEPTAL AREA AND NUCLEUS BASALIS MAGNOCELLULARIS {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({7}), pp. {4507-4519} 
    article  
    Abstract: The effects on anatomy and behavior of a ribosomal inactivating protein (saporin) coupled to a monoclonal antibody against the low-affinity NGF receptor (NGFr) were examined. In adult rats, NGFr is expressed predominantly in cholinergic neurons of the medial septal area (MSA), diagonal band nuclei, and nucleus basalis magnocellularis (nBM), but also in noncholinergic cerebellar Purkinje cells. Rats with immunotoxin injections to the MSA, nBM, and lateral ventricle were compared to controls on a spatial and cued reference memory task in the Morris maze. Toxin injections to the MSA slightly impaired the initial, but not asymptotic, phase of spatial navigation. injections to the nBM impaired all phases of spatial navigation. Cued navigation, however, was not affected in either the MSA or nBM group. The ventricular injections severely affected spatial and cued navigation. Acetylcholinesterase (AChE) histochemistry and NGFr and choline acetyltransferase immunohistochemistry revealed a loss of(l)almost all NGFr-positive cholinergic neurons in the MSA and AChE fibers in hippocampus (MSA group); (2) almost all NGFr neurons in the nBM, some in the MSA, most AChE fibers in neocortex and some in the hippocampus (nBM group), and (3) almost all NGFr neurons in the MSA and nBM and their corresponding hippocampal and cortical AChE fibers (ventricular group). Cholinergic nBM projections to the amygdala were largely preserved in all groups. The amount of cholinergic fiber loss in the cortex correlated modestly, but significantly, with the severity of impairment of the asymptotic phase of performance of the spatial task. An unambiguous interpretation of the anatomical locus of behavioral deficits was not possible because of damage to cholinergic striatal interneurons (nBM group) and to noncholinergic cerebellar Purkinje cells (ventricular group). These data suggest that the cholinergic,cortical system is critical to the performance of this spatial memory task. Cholinergic denervation of the hippocampus alone, however, is not sufficient to impair markedly performance of this task.
    BibTeX:
    @article{BERGERSWEENEY1994,
      author = {BERGERSWEENEY, J and HECKERS, S and MESULAM, MM and WILEY, RG and LAPPI, DA and SHARMA, M},
      title = {DIFFERENTIAL-EFFECTS ON SPATIAL NAVIGATION OF IMMUNOTOXIN-INDUCED CHOLINERGIC LESIONS OF THE MEDIAL SEPTAL AREA AND NUCLEUS BASALIS MAGNOCELLULARIS},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {7},
      pages = {4507-4519}
    }
    
    Berman, D. & Dudai, Y. Memory extinction, learning anew, and learning the new: Dissociations in the molecular machinery of learning in cortex {2001} SCIENCE
    Vol. {291}({5512}), pp. {2417-2419} 
    article  
    Abstract: The rat insular cortex (IC) subserves the memory of conditioned taste aversion (CTA), in which a taste is associated with malaise. When the conditioned taste is unfamiliar, formation of Long-term CTA memory depends on muscarinic and beta -adrenergic receptors, mitogen-activated protein kinase (MAPK), and protein synthesis. We show that extinction of CTA memory is also dependent on protein synthesis and beta -adrenergic receptors in the IC, but independent of muscarinic receptors and MAPK. This resembles the molecular signature of the formation of Long-term memory of CTA to a familiar taste. Thus, memory extinction shares molecular mechanisms with Learning, but the mechanisms of learning anew differ from those of Learning the new.
    BibTeX:
    @article{Berman2001,
      author = {Berman, DE and Dudai, Y},
      title = {Memory extinction, learning anew, and learning the new: Dissociations in the molecular machinery of learning in cortex},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {2001},
      volume = {291},
      number = {5512},
      pages = {2417-2419}
    }
    
    BERNARD, J., ALDEN, M. & BESSON, J. THE ORGANIZATION OF THE EFFERENT PROJECTIONS FROM THE PONTINE PARABRACHIAL AREA TO THE AMYGDALOID COMPLEX - A PHASEOLUS-VULGARIS LEUKOAGGLUTININ (PHA-L) STUDY IN THE RAT {1993} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {329}({2}), pp. {201-229} 
    article  
    Abstract: The organization of the efferent projections from the pontine parabrachial (pPB) area to the amygdala has been studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin (PHA-L), a sensitive and selective anterograde axonal marker, into restricted subregions of the pPB area. The results confirmed that the pPB area primarily projected onto the ipsilateral nucleus centralis of the amygdala (Ce), and to a lesser extent onto the ipsilateral posterior basolateral (BLP), anterior basomedial (BMA), and amygdaloid cortical (ACo) nuclei of the amygdala. Substantial projections were also found in the substantia innominata dorsal/ventral portion of the globus pallidus (SId/GPv), substriatal (SStr), and fondus striatal (FStr) regions which continue the amygdala rostrally. The results demonstrated that the projections of the pPB area onto the Ce were topically organized: 1) The region of the pPB area mainly including the medial subnucleus (pPBm), the waist area (pPBwa), and a thin rostral lamina of the ventral lateral subnucleus (pPBvl) projects primarily to the medial portion of the Ce (CeM). Dense projections were also found in the BLP, BMA, and ACo nuclei of the amygdala, and in the SId/GPv, SStr, and FStr rostral areas. 2) The region of the pPB mainly including the rostral portion of the central lateral subnucleus (pPBcl) and the outer-rostral portion of the external lateral subnucleus (pPBel) projects primarily to the lateral portion of the Ce (CeL). 3) The region of the pPB mainly including the dorsolateral subnucleus (pPBdl), the remaining pPBel, and the external medial (pPBem) subnuclei projects primarily to the lateral capsular portion of the Ce (CeLC) and bilaterally to its rostral portion. Dense projections were also found in the regions which extend the CeLC rostrally and in the SId/GPv, SStr, and FStr rostral areas. The possible role of each of the three parabrachio-amygdaloid pathways described is discussed. It was suggested that the pPB-CeM pathway is mainly implicated in gustatory processes; the pPB-CeL pathway is mainly implicated in visceral and chemosensitive processes; and the pPB-CeLC pathway is mainly implicated in respiratory, cardiovascular, and nociceptive processes.
    BibTeX:
    @article{BERNARD1993,
      author = {BERNARD, JF and ALDEN, M and BESSON, JM},
      title = {THE ORGANIZATION OF THE EFFERENT PROJECTIONS FROM THE PONTINE PARABRACHIAL AREA TO THE AMYGDALOID COMPLEX - A PHASEOLUS-VULGARIS LEUKOAGGLUTININ (PHA-L) STUDY IN THE RAT},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1993},
      volume = {329},
      number = {2},
      pages = {201-229}
    }
    
    Berridge, K. Food reward: Brain substrates of wanting and liking {1996} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {20}({1}), pp. {1-25} 
    article  
    Abstract: What are the neural substrates of food reward? Are reward and pleasure identical? Can taste pleasure be assessed in animals? Is reward necessarily conscious? These questions have re-emerged in recent years, and there is now sufficient evidence to prompt re-examination of many preconceptions concerning reward and its relation to brain systems. This paper reviews evidence from many sources regarding both the psychological structure of food reward and the neural systems that mediate it. Special attention is paid to recent evidence from `'taste reactivity'' studies of affective reactions to food. I argue that this evidence suggests the following surprising possibilities regarding the functional components and brain substrates of food reward. (1) Reward contains distinguishable psychological or functional components-''liking'' (pleasure/palatability) and `'wanting'' (appetite/incentive motivation). These can be manipulated and measured separately. (2) Liking and wanting have separable neural substrates. Mediation of liking related to food reward involves neurotransmitter systems such as opioid and GABA/benzodiazepine systems, and anatomical structures such as ventral pallidum and brainstem primary gustatory relays. Mediation of wanting related to food reward involves mesotelencephalic dopamine systems, and divisions of nucleus accumbens and amygdala. Both liking and wanting arise from vastly distributed neural systems, but the two systems are separable. (3) Neural processing of food reward is not confined to the limbic forebrain. Aspects of food reward begin to be processed in the brainstem. A neural manipulation can enhance reward or produce aversion but no single lesion or transection is likely abolish all properties of food reward. (4) Both wanting and liking can exist without subjective awareness. Conscious experience can distort or blur the underlying reward processes that gave rise to it. Subjective reports may contain false assessments of underlying processes, or even fail at all to register important reward processes. The core processes of liking and wanting that constitute reward are distinct from the subjective report or conscious awareness of those processes.
    BibTeX:
    @article{Berridge1996,
      author = {Berridge, KC},
      title = {Food reward: Brain substrates of wanting and liking},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1996},
      volume = {20},
      number = {1},
      pages = {1-25}
    }
    
    Berridge, K. & Robinson, T. Parsing reward {2003} TRENDS IN NEUROSCIENCES
    Vol. {26}({9}), pp. {507-513} 
    article DOI  
    Abstract: Advances in neurobiology permit neuroscientists to manipulate specific brain molecules, neurons and systems. This has lead to major advances in the neuroscience of reward. Here, it is argued that further advances will require equal sophistication in parsing reward into its specific psychological components: (1) learning (including explicit and implicit knowledge produced by associative conditioning and cognitive processes); (2) affect or emotion (implicit `liking' and conscious pleasure) and (3) motivation (implicit incentive salience `wanting' and cognitive incentive goals). The challenge is to identify how different brain circuits mediate different psychological components of reward, and how these components interact.
    BibTeX:
    @article{Berridge2003,
      author = {Berridge, KC and Robinson, TE},
      title = {Parsing reward},
      journal = {TRENDS IN NEUROSCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {2003},
      volume = {26},
      number = {9},
      pages = {507-513},
      doi = {{10.1016/S0166-2236(03)00233-9}}
    }
    
    Bhatnagar, S. & Dallman, M. Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress {1998} NEUROSCIENCE
    Vol. {84}({4}), pp. {1025-1039} 
    article  
    Abstract: Animals exposed to chronic stress exhibit normal or enhanced hypothalamic-pituitary-adrenal responses to novel, acute stimuli despite the inhibitory endogenous corticosteroid response to the chronic stressor. Prior stress is thought to induce a central facilitatory trace that, upon exposure to a novel stimulus, balances or overcomes the inhibitory effects of corticosterone. The neuroanatomical basis for this facilitation of hypothalamic-pituitary-adrenal responses is unknown. In this study, we first show increased adrenocorticotropin and corticosterone responses to the novel stressor of restraint in rats exposed to intermittent cold for seven days. We then compared numbers of Fos-immunoreactive cells in 26 sites in control and chronically stressed rats at various times after onset of a 30 min restraint. At 60 min, density of Fos-stained cells was significantly higher in chronically stressed than in control rats in the parabrachial/Kolliker-Fuse area, posterior paraventricular thalamus, central, basolateral and basomedial nuclei of the amygdala and parvocellular paraventricular hypothalamus. The posterior paraventricular nucleus of the thalamus receives projections from the parabrachial nucleus and projects heavily to the differentially stained subnuclei of the amygdala, which in turn project to the parvocellular paraventricular nucleus of the hypothalamus. We propose that increased activity in the parabrachial-posterior paraventricular thalamus-amypdala-parvocellular paraventricular hypo thalamus underlies facilitation of the hypothalamic-pituitary-adrenal axis to novel stress in chronically stressed rats. We confirmed part of this proposal by showing that lesions of the posterior paraventricular nucleus of the thalamus increase adrenocorticotropin responses to restraint only in previously chronically stressed animals. This potential circuit provides a basis for further examination of the functional roles of these regions in stress-induced facilitation of hypothalamic-pituitary-adrenal activity. (C) 1998 IBRO. Published by Elsevier Science Ltd.
    BibTeX:
    @article{Bhatnagar1998,
      author = {Bhatnagar, S and Dallman, M},
      title = {Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1998},
      volume = {84},
      number = {4},
      pages = {1025-1039}
    }
    
    Billings, L., Oddo, S., Green, K., McGaugh, J. & LaFerla, F. Intraneuronal A beta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice {2005} NEURON
    Vol. {45}({5}), pp. {675-688} 
    article DOI  
    Abstract: Progressive memory loss and cognitive dysfunction are the hallmark clinical features of Alzheimer's disease (AD). Identifying the molecular triggers for the onset of AD-related cognitive decline presently requires the use of suitable animal models, such as the 3xTg-AD mice, which develop both amyloid and tangle pathology. Here, we characterize the onset of learning and memory deficits in this model. We report that 2-month-old, prepathologic mice are cognitively unimpaired. The earliest cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal AD in the hippocampus and amygdala. Plaque or tangle pathology is not apparent at this age, suggesting that they contribute to cognitive dysfunction at later time points. Clearance of the intraneuronal AD pathology by immunotherapy rescues the early cognitive deficits on a hippocampal-dependent task. Reemergence of the AD pathology again leads to cognitive deficits. This study strongly implicates intraneuronal AD in the onset of cognitive dysfunction.
    BibTeX:
    @article{Billings2005,
      author = {Billings, LM and Oddo, S and Green, KN and McGaugh, JL and LaFerla, FM},
      title = {Intraneuronal A beta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2005},
      volume = {45},
      number = {5},
      pages = {675-688},
      doi = {{10.1016/j.neuron.2005.01.040}}
    }
    
    Blair, H., Schafe, G., Bauer, E., Rodrigues, S. & LeDoux, J. Synaptic plasticity in the lateral amygdala: A cellular hypothesis of fear conditioning {2001} LEARNING & MEMORY
    Vol. {8}({5}), pp. {229-242} 
    article  
    Abstract: Fear conditioning is a form of associative learning in which subjects come to express defense responses to a neutral conditioned stimulus (CS) that is paired with an aversive unconditioned stimulus (US). Considerable evidence suggests that critical neural changes mediating the CS-US association occur in the lateral nucleus of the amygdala (LA). Further, recent studies show that associative long-term potentiation (LTP) occurs in pathways that transmit the CS to LA, and that drugs that interfere with this LTP also disrupt behavioral fear conditioning when infused into the LA, suggesting that associative LTP in LA might be a mechanism for storing memories of the CS-US association. Here, we develop a detailed cellular hypothesis to explain how neural responses to the CS and US in LA could induce LTP-like changes that store memories during fear conditioning. Specifically, we propose that the CS evokes EPSPs at sensory input synapses onto LA pyramidal neurons, and that the US strongly depolarizes these same LA neurons. This depolarization, in turn, causes calcium influx through NMDA receptors (NMDARs) and also causes the LA neuron to fire action potentials. The action potentials then back-propagate into the dendrites, where they collide with CS-evoked EPSPs, resulting in calcium entry through voltage-gated calcium channels (VGCCs). Although calcium entry through NMDARs is sufficient to induce synaptic changes that support short-term fear memory, calcium entry through both NMDARs and VGCCs is required to initiate the molecular processes that consolidate synaptic changes into a long-term memory.
    BibTeX:
    @article{Blair2001,
      author = {Blair, HT and Schafe, GE and Bauer, EP and Rodrigues, SM and LeDoux, JE},
      title = {Synaptic plasticity in the lateral amygdala: A cellular hypothesis of fear conditioning},
      journal = {LEARNING & MEMORY},
      publisher = {COLD SPRING HARBOR LAB PRESS},
      year = {2001},
      volume = {8},
      number = {5},
      pages = {229-242}
    }
    
    Blair, R. & Cipolotti, L. Impaired social response reversal - A case of `acquired sociopathy' {2000} BRAIN
    Vol. {123}({Part 6}), pp. {1122-1141} 
    article  
    Abstract: In this study, we report a patient (J.S.) who, following trauma to the right frontal region, including the orbitofrontal cortex, presented with `acquired sociopathy'. His behaviour was notably aberrant and marked by high levels of aggression and a callous disregard for others. A series of experimental investigations were conducted to address the cognitive dysfunction that might underpin his profoundly aberrant behaviour. His performance was contrasted with that of a second patient (C.L.A.), who also presented with a grave dysexecutive syndrome but no socially aberrant behaviour, and five inmates of Wormwood Scrubs prison with developmental psychopathy. While J.S. showed no reversal learning impairment, he presented with severe difficulty in emotional expression recognition, autonomic responding and social cognition. Unlike the comparison populations, J.S. showed impairment in: the recognition of, and autonomic responding to, angry and disgusted expressions; attributing the emotions of fear, anger and embarrassment to story protagonists; and the identification of violations of social behaviour. The findings are discussed with reference to models regarding the role of the orbitofrontal cortex in the control of aggression. It is suggested that J.S.'s impairment is due to a reduced ability to generate expectations of others' negative emotional reactions, in particular anger. In healthy individuals, these representations act to suppress behaviour that is inappropriate in specific social contexts. Moreover, it is proposed that the orbitofrontal cortex may be implicated specifically either in the generation of these expectations or the use of these expectations to suppress inappropriate behaviour.
    BibTeX:
    @article{Blair2000,
      author = {Blair, RJR and Cipolotti, L},
      title = {Impaired social response reversal - A case of `acquired sociopathy'},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {2000},
      volume = {123},
      number = {Part 6},
      pages = {1122-1141}
    }
    
    Blair, R., Morris, J., Frith, C., Perrett, D. & Dolan, R. Dissociable neural responses to facial expressions of sadness and anger {1999} BRAIN
    Vol. {122}({Part 5}), pp. {883-893} 
    article  
    Abstract: Previous neuroimaging and neuropsychological studies have investigated the neural substrates which mediate responses to fearful, disgusted and happy expressions, No previous studies have investigated the neural substrates which mediate responses to sad and angry expressions. Using functional neuroimaging, we tested two hypotheses. First, we tested whether the amygdala has a neural response to sad and/or angry facial expressions. Secondly, we tested whether the orbitofrontal cortex has a specific neural response to angry facial expressions. Volunteer subjects were scanned, using PET, while they performed a sex discrimination task involving static grey-scale images of faces expressing varying degrees of sadness and anger. We found that increasing intensity of sad facial expression was associated with enhanced activity in the left amygdala and right temporal pole. In addition, we found that increasing intensity of angry facial expression was associated with enhanced activity in the orbitofrontal and anterior cingulate cortex. We found no support for the suggestion that angry expressions generate a signal in the amygdala, The results provide evidence for dissociable, but interlocking, systems for the processing of distinct categories of negative facial expression.
    BibTeX:
    @article{Blair1999,
      author = {Blair, RJR and Morris, JS and Frith, CD and Perrett, DI and Dolan, RJ},
      title = {Dissociable neural responses to facial expressions of sadness and anger},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {1999},
      volume = {122},
      number = {Part 5},
      pages = {883-893}
    }
    
    Blood, A. & Zatorre, R. Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({20}), pp. {11818-11823} 
    article  
    Abstract: We used positron emission tomography to study neural mechanisms underlying intensely pleasant emotional responses to music. Cerebral blood flow changes were measured in response to subject-selected music that elicited the highly pleasurable experience of ``shivers-down-the-spine'' or ``chills.'' Subjective reports of chills were accompanied by changes in heart rate, electromyogram, and respiration. As intensity of these chills increased, cerebral blood flow increases and decreases were observed in brain regions thought to be involved in reward/motivation, emotion, and arousal, including ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex. These brain structures are known to be active in response to other euphoria-inducing stimuli, such as food, sex, and drugs of abuse. This finding links music with biologically relevant, survival-related stimuli via their common recruitment of brain circuitry involved in pleasure and reward.
    BibTeX:
    @article{Blood2001,
      author = {Blood, AJ and Zatorre, RJ},
      title = {Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {2001},
      volume = {98},
      number = {20},
      pages = {11818-11823}
    }
    
    Blood, A., Zatorre, R., Bermudez, P. & Evans, A. Emotional responses to pleasant and unpleasant music correlate with activity in paralimbic brain regions {1999} NATURE NEUROSCIENCE
    Vol. {2}({4}), pp. {382-387} 
    article  
    Abstract: Neural correlates of the often-powerful emotional responses to music are poorly understood. Here we used positron emission tomography to examine cerebral blood flow (CBF) changes related to affective responses to music. Ten volunteers were scanned while listening to six versions of a novel musical passage varying systematically in degree of dissonance. Reciprocal CBF covariations were observed in several distinct paralimbic and neocortical regions as a function of dissonance and of perceived pleasantness/unpleasantness. The findings suggest that music may recruit neural mechanisms similar to those previously associated with pleasant/unpleasant emotional states, but different from those underlying other components of music perception, and other emotions such as fear.
    BibTeX:
    @article{Blood1999,
      author = {Blood, AJ and Zatorre, RJ and Bermudez, P and Evans, AC},
      title = {Emotional responses to pleasant and unpleasant music correlate with activity in paralimbic brain regions},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {1999},
      volume = {2},
      number = {4},
      pages = {382-387}
    }
    
    BOGERTS, B. RECENT ADVANCES IN THE NEUROPATHOLOGY OF SCHIZOPHRENIA {1993} SCHIZOPHRENIA BULLETIN
    Vol. {19}({2}), pp. {431-445} 
    article  
    Abstract: This article reviews some 50 neuroanatomical postmortem studies published in the last 20 years. The majority of these studies demonstrated various types of subtle anomalies in limbic structures, that is, the hippocampus, parahippocampal gyrus, entorhinal cortex, amygdala, cingulate gyrus, and septum of schizophrenia patients. A number of schizophrenic symptoms might be related to structural and functional disturbances of these brain regions. But these studies also reported subtle changes in parts of the basal ganglia, thalamus, cortex, corpus callosum, and brainstem neurotransmitter systems. Many of the studies, however, are based on small sample sizes and, therefore, must be regarded as preliminary. Cytoarchitectonic abnormalities and lack of gliosis in limbic structures as well as the absence of normal structural cerebral asymmetry in a substantial proportion of patients indicate that these structural anomalies may reflect a disorder of prenatal brain development and argue against the notion that schizophrenia is a progressive degenerative brain disorder.
    BibTeX:
    @article{BOGERTS1993,
      author = {BOGERTS, B},
      title = {RECENT ADVANCES IN THE NEUROPATHOLOGY OF SCHIZOPHRENIA},
      journal = {SCHIZOPHRENIA BULLETIN},
      publisher = {US GOVERNMENT PRINTING OFFICE},
      year = {1993},
      volume = {19},
      number = {2},
      pages = {431-445}
    }
    
    BOGERTS, B., LIEBERMAN, J., ASHTARI, M., BILDER, R., DEGREEF, G., LERNER, G., JOHNS, C. & MASIAR, S. HIPPOCAMPUS AMYGDALA VOLUMES AND PSYCHOPATHOLOGY IN CHRONIC-SCHIZOPHRENIA {1993} BIOLOGICAL PSYCHIATRY
    Vol. {33}({4}), pp. {236-246} 
    article  
    Abstract: Volumes of the mesiotemporal structures (hippocampus-amygdala complex) were measured in 19 men who were chronic multiepisode schizophrenics and 18 age-matched healthy controls using Tl-weighted contiguous coronal magnetic resonance images of 3.1-mm width. Using the level of the mammillary bodies as an anatomical landmark, the whole hippocampus-amygdala complex was divided into an anterior section (mainly containing amygdaloid tissue) and a posterior section (mainly containing the hippocampal formation). Total mesiotemporal tissue volume was reduced significantly in the patient group compared to controls (-11, with significant reductions in both left (-20 and right (-15 hippocampal sections. Reduced limbic tissue volume was associated with increased severity of psychopathology. Severity of positive psychotic symptoms (Brief Psychiatric Rating Scale [BPRS] psychosis factor) was correlated significantly with right and left total mesiotemporal volumes (Spearman rho's = -0.61 p < 0.01). Negative symptom scores (BPRS anergia factor, Scale for Assessment of Negative Symptoms [SANS] global items) were not significantly correlated with any mesiotemporal tissue volumes. The data corroborate and extend previous findings of temporolimbic structure volume reduction in schizophrenia, and suggest that the positive psychotic symptoms of schizophrenia are associated with anatomic anomalies in mesiotemporal structure.
    BibTeX:
    @article{BOGERTS1993a,
      author = {BOGERTS, B and LIEBERMAN, JA and ASHTARI, M and BILDER, RM and DEGREEF, G and LERNER, G and JOHNS, C and MASIAR, S},
      title = {HIPPOCAMPUS AMYGDALA VOLUMES AND PSYCHOPATHOLOGY IN CHRONIC-SCHIZOPHRENIA},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1993},
      volume = {33},
      number = {4},
      pages = {236-246}
    }
    
    Bonda, E., Petrides, M., Ostry, D. & Evans, A. Specific involvement of human parietal systems and the amygdala in the perception of biological motion {1996} JOURNAL OF NEUROSCIENCE
    Vol. {16}({11}), pp. {3737-3744} 
    article  
    Abstract: To explore the extent to which functional systems within the human posterior parietal cortex and the superior temporal sulcus are involved in the perception of action, we measured cerebral metabolic activity in human subjects by positron emission tomography during the perception of simulations of biological motion with point-light displays. The experimental design involved comparisons of activity during the perception of goal-directed hand action, whole body motion, object motion, and random motion. The results demonstrated that the perception of scripts of goal-directed hand action implicates the cortex in the intraparietal sulcus and the caudal part of the superior temporal sulcus, both in the left hemisphere. By contrast, the rostrocaudal part of the right superior temporal sulcus and adjacent temporal cortex, and limbic structures such as the amygdala, are involved in the perception of signs conveyed by expressive body movements.
    BibTeX:
    @article{Bonda1996,
      author = {Bonda, E and Petrides, M and Ostry, D and Evans, A},
      title = {Specific involvement of human parietal systems and the amygdala in the perception of biological motion},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1996},
      volume = {16},
      number = {11},
      pages = {3737-3744}
    }
    
    Borowsky, B., Adham, N., Jones, K., Raddatz, R., Artymyshyn, R., Ogozalek, K., Durkin, M., Lakhlani, P., Bonini, J., Pathirana, S., Boyle, N., Pu, X., Kouranova, E., Lichtblau, H., Ochoa, F., Branchek, T. & Gerald, C. Trace amines: Identification of a family of mammalian G protein-coupled receptors {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({16}), pp. {8966-8971} 
    article  
    Abstract: Tyramine, beta -phenylethylamine, tryptamine, and octopamine are biogenic amines present in trace levels in mammalian nervous systems. Although some ``trace amines have dearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Using a degenerate PCR approach, we have identified 15 G protein-coupled receptors (GPCR) from human and rodent tissues. Together with the orphan receptor PNR, these receptors form a subfamily of rhodopsin GPCRs distinct from, but related to the classical biogenic amine receptors. We have demonstrated that two of these receptors bind and/or are activated by trace amines. The cloning of mammalian GPCRs for trace amines supports a role for trace amines as neurotransmitters in vertebrates. Three of the four human receptors from this family are present in the amygdala, possibly linking trace amine receptors to affective disorders. The identification of this family of receptors should rekindle the investigation of the roles of trace amines in mammalian nervous systems and may potentially lead to the development of novel therapeutics for a variety of indications.
    BibTeX:
    @article{Borowsky2001,
      author = {Borowsky, B and Adham, N and Jones, KA and Raddatz, R and Artymyshyn, R and Ogozalek, KL and Durkin, MM and Lakhlani, PP and Bonini, JA and Pathirana, S and Boyle, N and Pu, XS and Kouranova, E and Lichtblau, H and Ochoa, FY and Branchek, TA and Gerald, C},
      title = {Trace amines: Identification of a family of mammalian G protein-coupled receptors},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {2001},
      volume = {98},
      number = {16},
      pages = {8966-8971}
    }
    
    BRAAK, E., BRAAK, H. & MANDELKOW, E. A SEQUENCE OF CYTOSKELETON CHANGES RELATED TO THE FORMATION OF NEUROFIBRILLARY TANGLES AND NEUROPIL THREADS {1994} ACTA NEUROPATHOLOGICA
    Vol. {87}({6}), pp. {554-567} 
    article  
    Abstract: Frontal sections of the temporal lobe including the transentorhinal/entorhinal region, amygdala, and/or hippocampus from human adult brains are studied for cytoskeleton changes using immunostaining with the antibodies AT8 and Alz-50 and selective silver impregnation methods for neurofibrillary changes of the Alzheimer type. For the purpose of correlation, the two methods are carried out one after the other on the same section. Layer pre-alpha in the transentorhinal/entorhinal region harbours nerve cells which are among the first nerve cells in the entire brain to show the development of neurofibrillary changes. This presents the opportunity for study of both early events in the destruction of the cytoskeleton in individual neurons, and to relate changes which occur in the neuronal processes in the absence of alterations in their immediate surroundings to those happening in the soma. Immunoreactions with the AT8 antibody in particular reveal a clear sequence of changes in the neuronal cytoskeleton. Group 1 neurons present initial cytoskeleton changes in that the soma, dendrites, and axon are completely marked by granular AT8 immunoreactive material. These neurons appear quite normal and turn out to be devoid of argyrophilic material when observed in silver-stained sections. Group 2 neurons show changes in the cellular processes. The terminal tuft of the apical dendrite is replaced by tortuous varicose fibres and coarse granules. The distal protions of the dendrites are curved and show appendages and thickened portions. Intensely homogeneously immunostained rod-like inclusions are encountered in these thickened portions and in the soma. A number of these rod-like inclusions are visible after silver staining, as well. Group 3 neurons display even more pronounced alterations of their distal - most dendritic portions. The intermediate dendritic parts lose immunoreactivity, but the soma is homogeneously immunostained. Silver staining reveals in most of the distal dendritic parts neuropil threads, and in the soma a classic neurofibrillary tangle. Group 4 structures are marked by accumulations of coarse AT8-immunoreactive granules. Silver staining provides evidence that the fibrillary material has become an extraneuronal, `'early'' ghost tangle. Finally, group 5 structures present `'late'' ghost tangles in silver-stained sections but fail to demonstrate AT8 immunoreactivity. It is suggested that the altered tau protein shown by the antibody AT8 represents an early cytoskeleton change which eventually leads to the formation of argyrophilic neurofibrillary tangles and neuropil threads.
    BibTeX:
    @article{BRAAK1994,
      author = {BRAAK, E and BRAAK, H and MANDELKOW, EM},
      title = {A SEQUENCE OF CYTOSKELETON CHANGES RELATED TO THE FORMATION OF NEUROFIBRILLARY TANGLES AND NEUROPIL THREADS},
      journal = {ACTA NEUROPATHOLOGICA},
      publisher = {SPRINGER VERLAG},
      year = {1994},
      volume = {87},
      number = {6},
      pages = {554-567}
    }
    
    Brambilla, R., Gnesutta, N., Minichiello, L., White, G., Roylance, A., Herron, C., Ramsey, M., Wolfer, D., Cestari, V., RossiArnaud, C., Grant, S., Chapman, P., Lipp, H., Sturani, E. & Klein, R. A role for the Ras signalling pathway in synaptic transmission and long-term memory {1997} NATURE
    Vol. {390}({6657}), pp. {281-286} 
    article  
    Abstract: Members of the Ras subfamily of small guanine-nucleotide-binding proteins are essential for controlling normal and malignant cell proliferation as well as cell differentiation(1). The neuronal-specific guanine-nucleotide-exchange factor, Ras-GRF/CDC25Mm (refs 2-4), induces Ras signalling in response to Ca2+ influx(5) and activation of G-protein-coupled receptors in vitro(6), suggesting that it plays a role in neurotransmission and plasticity in vivo(7). Here we report that mice lacking Ras-GRF are impaired in the process of memory consolidation, as revealed by emotional conditioning tasks that require the function of the amygdala; learning and short-term memory are intact. Electrophysiological measurements in the basolateral amygdala reveal that long-term plasticity is abnormal in mutant mice. In contrast, Ras-GRF mutants do not reveal major deficits in spatial learning tasks such as the Morris water maze, a test that requires hippocampal function. Consistent with apparently normal hippocampal functions, Ras-GRF mutants show normal NMDA (N-methyl-D-aspartate) receptor-dependent long-term potentiation in this structure. These results implicate Ras-GRF signalling via the Ras/MAP kinase pathway in synaptic events leading to formation of long-term memories.
    BibTeX:
    @article{Brambilla1997,
      author = {Brambilla, R and Gnesutta, N and Minichiello, L and White, G and Roylance, AJ and Herron, CE and Ramsey, M and Wolfer, DP and Cestari, V and RossiArnaud, C and Grant, SGN and Chapman, PF and Lipp, HP and Sturani, E and Klein, R},
      title = {A role for the Ras signalling pathway in synaptic transmission and long-term memory},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1997},
      volume = {390},
      number = {6657},
      pages = {281-286}
    }
    
    BREDER, C., DEWITT, D. & KRAIG, R. CHARACTERIZATION OF INDUCIBLE CYCLOOXYGENASE IN RAT-BRAIN {1995} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {355}({2}), pp. {296-315} 
    article  
    Abstract: Considerable debate exists regarding the cellular source of prostaglandins in the mammalian central nervous system (CNS). At least two forms of prostaglandin endoperoxide synthase, or cyclooxygenase (COX), the principal enzyme in the biosynthesis of these mediators, are known to exist. Both forms have been identified in the CNS, but only the distribution of COX 1 has been mapped in detail. In this study, we used Western blot analysis and immunohistochemistry to describe the biochemical characterization and anatomical distribution of the second, mitogen-inducible form of this enzyme, COX 2 in the rat brain. COX 2-like immunoreactive (COX 2-ir) staining occurred in dendrites and cell bodies of neurons, structures that are typically postsynaptic. It was noted in distinct portions of specific cortical laminae and subcortical nuclei. The distribution in the CNS was quite different from COX 1. COX 2-ir neurons were primarily observed in the cortex and allocortical structures, such as the hippocampal formation and amygdala. Within the amygdala, neurons were primarily observed in the caudal and posterior part of the deep and cortical nuclei. In the diencephalon, COX 2-ir cells were also observed in the paraventricular nucleus of the hypothalamus and in the nuclei of the anteroventral region surrounding the third ventricle, including the vascular organ of the lamina terminalis. COX 2-ir neurons were also observed in the subparafascicular nucleus, the medial zona incerta, and pretectal area. In the brainstem, COX 2-ir neurons were observed in the dorsal raphe nucleus, the nucleus of the brachium of the inferior colliculus, and in the region of the subcoeruleus. The distribution of COX 2-ir neurons in the CNS suggests that COX 2 may be involved in processing and integration of visceral and special sensory input and in elaboration of the autonomic, endocrine, and behavioral responses. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{BREDER1995,
      author = {BREDER, CD and DEWITT, D and KRAIG, RP},
      title = {CHARACTERIZATION OF INDUCIBLE CYCLOOXYGENASE IN RAT-BRAIN},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1995},
      volume = {355},
      number = {2},
      pages = {296-315}
    }
    
    BREIER, A., BUCHANAN, R., ELKASHEF, A., MUNSON, R., KIRKPATRICK, B. & GELLAD, F. BRAIN MORPHOLOGY AND SCHIZOPHRENIA - A MAGNETIC-RESONANCE-IMAGING STUDY OF LIMBIC, PREFRONTAL CORTEX, AND CAUDATE STRUCTURES {1992} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {49}({12}), pp. {921-926} 
    article  
    Abstract: We used magnetic resonance imaging to examine the morphologic characteristics of the amygdala/hippocampus, prefrontal cortex, and caudate nucleus in 29 healthy volunteers matched for age, gender, and head of household socioeconomic status and 44 patients with chronic schizophrenia. Total volumes of these structures were determined from 3-mm contiguous coronal sections. Schizophrenic patients, compared with healthy controls, had significantly smaller right and left amygdala/hippocampal complex volumes, smaller right and left prefrontal volumes, and larger left caudate volumes. A secondary analysis revealed reductions in the right and left amygdala and the left hippocampus. In addition, prefrontal white matter, but not gray matter, was reduced in the schizophrenic patients. Moreover, the right white matter volume in schizophrenic patients was significantly related to right amygdala/hippocampal volume (r=.39), data that provide preliminary support for a hypothesis of abnormal limbic-cortical connection in schizophrenia. We studied the implications of these data for the pathophysiology of schizophrenia.
    BibTeX:
    @article{BREIER1992,
      author = {BREIER, A and BUCHANAN, RW and ELKASHEF, A and MUNSON, RC and KIRKPATRICK, B and GELLAD, F},
      title = {BRAIN MORPHOLOGY AND SCHIZOPHRENIA - A MAGNETIC-RESONANCE-IMAGING STUDY OF LIMBIC, PREFRONTAL CORTEX, AND CAUDATE STRUCTURES},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      publisher = {AMER MEDICAL ASSOC},
      year = {1992},
      volume = {49},
      number = {12},
      pages = {921-926}
    }
    
    Breiter, H., Aharon, I., Kahneman, D., Dale, A. & Shizgal, P. Functional imaging of neural responses to expectancy and experience of monetary gains and losses {2001} NEURON
    Vol. {30}({2}), pp. {619-639} 
    article  
    Abstract: Neural responses accompanying anticipation and experience of monetary gains and losses were monitored by functional magnetic resonance imaging. Trials comprised an initial ``prospect'' (expectancy) phase, when a set of three monetary amounts was displayed, and a subsequent ``outcome'' phase, when one of these amounts was awarded. Hemodynamic responses in the sublenticular extended amygdala (SLEA) and orbital gyrus tracked the expected values of the prospects, and responses to the highest value set of outcomes increased monotonically with monetary value in the nucleus accumbens, SLEA, and hypothalamus. Responses to prospects and outcomes were generally, but not always, seen in the same regions. The overlap of the observed activations with those seen previously in response to tactile stimuli, gustatory stimuli, and euphoria-inducing drugs is consistent with a contribution of common circuitry to the processing of diverse rewards.
    BibTeX:
    @article{Breiter2001,
      author = {Breiter, HC and Aharon, I and Kahneman, D and Dale, A and Shizgal, P},
      title = {Functional imaging of neural responses to expectancy and experience of monetary gains and losses},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2001},
      volume = {30},
      number = {2},
      pages = {619-639}
    }
    
    Breiter, H., Etcoff, N., Whalen, P., Kennedy, W., Rauch, S., Buckner, R., Strauss, M., Hyman, S. & Rosen, B. Response and habituation of the human amygdala during visual processing of facial expression {1996} NEURON
    Vol. {17}({5}), pp. {875-887} 
    article  
    Abstract: We measured amygdala activity in human volunteers during rapid visual presentations of fearful, happy, and neutral faces using functional magnetic resonance imaging (fMRI). The first experiment involved a fixed order of conditions both within and across runs, while the second one used a fully counterbalanced order in addition to a low level baseline of simple visual stimuli. In both experiments, the amygdala was preferentially activated in response to fearful versus neutral faces. In the counterbalanced experiment, the amygdala also responded preferentially to happy versus neutral faces, suggesting a possible generalized response to emotionally valenced stimuli. Rapid habituation effects were prominent in both experiments. Thus, the human amygdala responds preferentially to emotionally valenced faces and rapidly habituates to them.
    BibTeX:
    @article{Breiter1996,
      author = {Breiter, HC and Etcoff, NL and Whalen, PJ and Kennedy, WA and Rauch, SL and Buckner, RL and Strauss, MM and Hyman, SE and Rosen, BR},
      title = {Response and habituation of the human amygdala during visual processing of facial expression},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {1996},
      volume = {17},
      number = {5},
      pages = {875-887}
    }
    
    Breiter, H., Gollub, R., Weisskoff, R., Kennedy, D., Makris, N., Berke, J., Goodman, J., Kantor, H., Gastfriend, D., Riorden, J., Mathew, R., Rosen, B. & Hyman, S. Acute effects of cocaine on human brain activity and emotion {1997} NEURON
    Vol. {19}({3}), pp. {591-611} 
    article  
    Abstract: We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, Ventral tegmentum, and pens and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pens, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving.
    BibTeX:
    @article{Breiter1997,
      author = {Breiter, HC and Gollub, RL and Weisskoff, RM and Kennedy, DN and Makris, N and Berke, JD and Goodman, JM and Kantor, HL and Gastfriend, DR and Riorden, JP and Mathew, RT and Rosen, BR and Hyman, SE},
      title = {Acute effects of cocaine on human brain activity and emotion},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {1997},
      volume = {19},
      number = {3},
      pages = {591-611}
    }
    
    Breiter, H., Rauch, S., Kwong, K., Baker, J., Weisskoff, R., Kennedy, D., Kendrick, A., Davis, T., Jiang, A., Cohen, M., Stern, C., Belliveau, J., Baer, L., OSullivan, R., Savage, C., Jenike, M. & Rosen, B. Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder {1996} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {53}({7}), pp. {595-606} 
    article  
    Abstract: Background: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. Methods: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. Results: Statistical maps (nonparametric; P<10(-3)) showed activation for 70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects exhibited activation in any brain region. Conclusions: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study.
    BibTeX:
    @article{Breiter1996a,
      author = {Breiter, HC and Rauch, SL and Kwong, KK and Baker, JR and Weisskoff, RM and Kennedy, DN and Kendrick, AD and Davis, TL and Jiang, AP and Cohen, MS and Stern, CE and Belliveau, JW and Baer, L and OSullivan, RL and Savage, CR and Jenike, MA and Rosen, BR},
      title = {Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      publisher = {AMER MEDICAL ASSOC},
      year = {1996},
      volume = {53},
      number = {7},
      pages = {595-606}
    }
    
    Bremner, J., Narayan, M., Anderson, E., Staib, L., Miller, H. & Charney, D. Hippocampal volume reduction in major depression {2000} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {157}({1}), pp. {115-117} 
    article  
    Abstract: Objective: Elevated levels of glucocorticoids in depression have been hypothesized to be associated with damage to the hippocampus, a brain area involved in learning and memory. The purpose of this study was to measure hippocampal volume in patients with depression. Method: Magnetic resonance imaging was used to measure the volume of the hippocampus in 16 patients with major depression in remission and 16 case-matched nondepressed comparison subjects. Results: Patients with depression had a statistically significant 19% smaller left hippocampal volume than comparison subjects, without smaller volumes of comparison regions (amygdala, caudate, frontal lobe, and temporal lobe) or whole brain volume. The findings were significant after brain size, alcohol exposure, age, and education were controlled for. Conclusions: These findings are consistent with smaller left hippocampal volume in depression.
    BibTeX:
    @article{Bremner2000,
      author = {Bremner, JD and Narayan, M and Anderson, ER and Staib, LH and Miller, HL and Charney, DS},
      title = {Hippocampal volume reduction in major depression},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      publisher = {AMER PSYCHIATRIC PRESS, INC},
      year = {2000},
      volume = {157},
      number = {1},
      pages = {115-117}
    }
    
    Bremner, J., Randall, P., Vermetten, E., Staib, L., Bronen, R., Mazure, C., Capelli, S., McCarthy, G., Innis, R. & Charney, D. Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse - A preliminary report {1997} BIOLOGICAL PSYCHIATRY
    Vol. {41}({1}), pp. {23-32} 
    article  
    Abstract: We have previously reported smaller hippocampal volume and deficits in short-term memory in patients with combat-related posttraumatic stress disorder (PTSD) relative to comparison subjects. The purpose of this study was to compare hippocampal volume in adult survivors of childhood abuse to matched controls, Magnetic resonance imaging was used to measure volume of the hippocampus in adult survivors of childhood abuse (n = 17) and healthy subjects (n = 17) matched on a care-by-case basis for age, sex, race, handedness, years of education, body size, and years of alcohol abuse. All patients met criteria for PTSD secondary to childhood abuse, PTSD patients had a 12% smaller left hippocampal volume relative to the matched controls (p < .05), without smaller volumes of comparison regions (amygdala, caudate, and temporal lobe). The findings were significant after controlling for alcohol, age, and education, with multiple linear regression, These findings suggest that a decrease in Left hippocampal volume is associated with abuse-related PTSD. (C) 1997 Society of Biological Psychiatry.
    BibTeX:
    @article{Bremner1997,
      author = {Bremner, JD and Randall, P and Vermetten, E and Staib, L and Bronen, RA and Mazure, C and Capelli, S and McCarthy, G and Innis, RB and Charney, DS},
      title = {Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse - A preliminary report},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1997},
      volume = {41},
      number = {1},
      pages = {23-32}
    }
    
    Bremner, J., Staib, L., Kaloupek, D., Southwick, S., Soufer, R. & Charney, D. Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: A positron emission tomography study {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({7}), pp. {806-816} 
    article  
    Abstract: Background: Patients with posttraumatic stress disorder (PTSD) show a reliable increase in PTSD symptoms and physiological reactivity following exposure to traumatic pictures and sounds. In this study neural correlates of exposure to traumatic pictures and sounds were measured in PTSD. Methods: Positron emission tomography and H2[15O] were used to measure cerebral blood flow during exposure to combat-related and neutral pictures and sounds in Vietnam combat veterans with and without PTSD. Results: Exposure to traumatic material in PTSD (but not non-PTSD) subjects resulted in a decrease in blood flow in medial prefrontal cortex (area 25), an area postulated to play a role in emotion through inhibition of amygdala responsiveness. Non-PTSD subjects activated anterior cingulate (area 24) to a greater degree than PTSD patients. There were also differences in cerebral blood flow response in areas involved in memory and visuospatial processing (and by extension response to threat), including posterior cingulate (area 23), precentral (motor) and inferior parietal cortex, and lingual gyrus. There was a pattern of increases in PTSD and decreases in non-PTSD subjects in these areas. Conclusions: The findings suggest that functional alterations in specific cortical and subcortical brain areas involved in memory, visuospatial processing, and emotion underlie the symptoms of patients with PTSD. (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Bremner1999,
      author = {Bremner, JD and Staib, LH and Kaloupek, D and Southwick, SM and Soufer, R and Charney, DS},
      title = {Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: A positron emission tomography study},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1999},
      volume = {45},
      number = {7},
      pages = {806-816}
    }
    
    BROG, J., SALYAPONGSE, A., DEUTCH, A. & ZAHM, D. THE PATTERNS OF AFFERENT INNERVATION OF THE CORE AND SHELL IN THE ACCUMBENS PART OF THE RAT VENTRAL STRIATUM - IMMUNOHISTOCHEMICAL DETECTION OF RETROGRADELY TRANSPORTED FLUOROGOLD {1993} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {338}({2}), pp. {255-278} 
    article  
    Abstract: Recent data have emphasized the neurochemically distinct nature of subterritories in the accumbens part of the rat ventral striatum termed the core, shell, and rostral pole. In order to gain a more comprehensive understanding of how afferents are distributed relative to these subterritories, immunohistochemical detection of retrogradely transported Fluoro-Gold was carried out following iontophoretic injections intended to involve selectively one of the subterritories. The data revealed that a number of cortical afferents of the medial shell and core originate in separate areas, i.e., the dorsal peduncular, infralimbic, and posterior piriform cortices (to medial shell) and the dorsal prelimbic, anterior agranular insular, anterior cingulate, and perirhinal cortices (to core). The lateral shell and rostral pole are innervated by cortical structures that also project either to the medial shell or core. The orbital, posterior agranular insular, and entorhinal cortices, hippocampus, and basal amygdala were observed to innervate the accumbens in a topographic manner. Following core injections, strong bilateral cortical labeling was observed. Few labeled cortical cells were observed contralaterally following injections in the medial shell. Intermediate numbers of labeled neurons were observed in contralateral cortices following lateral shell injections. Robust subcortical labeling in a variety of structures in the ventral forebrain, lateral hypothalamus, deep temporal lobe, and brainstem was observed after shell injections, particularly those that involved the caudal dorsomedial extremity of the shell, i.e., its `'septal pole.'' Selective ipsilateral labeling of subcortical structures in the basal ganglia circuitry was observed following injections in the core and, to a lesser extent, lateral shell. It was concluded that a number of afferent systems exhibit varying degrees of segregation with respect to the accumbal subterritories. (C) 1993 Wiley-Liss, Inc.
    BibTeX:
    @article{BROG1993,
      author = {BROG, JS and SALYAPONGSE, A and DEUTCH, AY and ZAHM, DS},
      title = {THE PATTERNS OF AFFERENT INNERVATION OF THE CORE AND SHELL IN THE ACCUMBENS PART OF THE RAT VENTRAL STRIATUM - IMMUNOHISTOCHEMICAL DETECTION OF RETROGRADELY TRANSPORTED FLUOROGOLD},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1993},
      volume = {338},
      number = {2},
      pages = {255-278}
    }
    
    Brown, R., Stevens, D. & Haas, H. The physiology of brain histamine {2001} PROGRESS IN NEUROBIOLOGY
    Vol. {63}({6}), pp. {637-672} 
    article  
    Abstract: Histamine-releasing neurons are located exclusively ill thr TM of the hypothalamus. from where they project to practically all brain regions, with ventral areas (hypothalamus. basal Forebrain. amygdala) receiving a particularly strong innervation. The intrinsic electrophysiological properties of TM neurons (slow spontaneous firing, broad action potentials. deep afterhyperpolarisations, etc.) are extremely similar to other aminergic neurons. Their firing rate varies across the sleep-wake cycle. being highest during waking and lowest during rapid-eye movement sleep. In contrast to other aminergic neurons somatodendritic autoreceptors (H-3) do not activate atl inwardly rectifying potassium channel but instead control firing by inhibiting voltage-dependent calcium channels. Histamine release is enhanced under extreme conditions such as dehydration or hypoglycemia or by a variety of stressors. Histamine activates four types of receptors. H-1 receptors are mainly postsynaptically located and are coupled positively to phospholipase C. High densities are found especially in the hypothalamus and other limbic regions. Activation of these receptors causes large depolarisations via blockade of a leak potassium conductance. activation of a non-specific cation channel or activation of a sodium-calcium exchanger. H-2 receptors are also mainly postsynaptically located and are coupled positively to adenylyl cyclase. High densities are found in hippocampus. amygdala and basal ganglia. Activation of these receptors also leads to mainly excitatory effects through blockade of calcium-dependent potassium channels and modulation of the hyperpolarisation-activated cation channel, H-3 receptors are exclusively presynaptically located and are negatively coupled to adenylyl cyclase. High densities are found in the basal ganglia. These receptors mediated presynaptic inhibition of histamine release and the release of other neurotransmitters, most likely via inhibition of presynaptic calcium channels. Finally, histamine modulates the glutamate NMDA receptor via an action at the polyamine binding site. The central histamine system is involved in many central nervous system functions: arousal; anxiety; activation of the sympathetic nervous system. the stress-related release of hormones from the pituitary and of central aminergic neurotransmitters; antinociception; water retention and suppression of eating. A role for the neuronal histamine system as a danger response system is proposed. (C) 2001 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Brown2001,
      author = {Brown, RE and Stevens, DR and Haas, HL},
      title = {The physiology of brain histamine},
      journal = {PROGRESS IN NEUROBIOLOGY},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2001},
      volume = {63},
      number = {6},
      pages = {637-672}
    }
    
    BRUNO, J., XU, Y., SONG, J. & BERELOWITZ, M. TISSUE DISTRIBUTION OF SOMATOSTATIN RECEPTOR SUBTYPE MESSENGER-RIBONUCLEIC-ACID IN THE RAT {1993} ENDOCRINOLOGY
    Vol. {133}({6}), pp. {2561-2567} 
    article  
    Abstract: The tissue distribution of mRNA encoding five somatostatin receptor subtypes, SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5, was determined in adult rat tissues by solution hybridization/nuclease protection analysis using sequence-specific cRNA probes. In the central nervous system, SSTR1 and SSTR2 mRNA were expressed widely, with highest levels in hippocampus, hypothalamus, cortex, and amygdala and expression of both isoforms in cerebellum and spinal cord. Expression of SSTR3 was also widespread, occurring in all brain regions examined, with the highest level of expression in the cerebellum. SSTR4 mRNA was detected in most brain regions, with highest levels occurring in the hippocampus, cortex, and olfactory bulb. No detectable levels were found in cerebellum. SSTR5 showed a unique pattern of expression in the central nervous system, being found primarily in the hypothalamus and preoptic area. In peripheral tissues, high levels of SSTR1 and SSTR2 mRNA were found in pituitary and spleen. SSTR1 mRNA was also found in the heart and intestine, SSTR2 was detected in pancreas, and both isoforms were expressed in stomach. Expression of SSTR3 was noted in heart, liver, stomach, intestine, kidney, spleen, and pituitary. The patterns of expression were similar for SSTR4 and SSTR3 mRNA; however, SSTR4 was not expressed in liver. SSTR5 was expressed predominantly in the pituitary, but detectible levels were observed in spleen and intestine. Thus, the SSTR subtype mRNA showed both a tissue-specific and overlapping pattern of expression. Taken together with SSTR-specific signal transduction systems, this probably explains the diverse physiological actions of somatostatin.
    BibTeX:
    @article{BRUNO1993,
      author = {BRUNO, JF and XU, Y and SONG, JF and BERELOWITZ, M},
      title = {TISSUE DISTRIBUTION OF SOMATOSTATIN RECEPTOR SUBTYPE MESSENGER-RIBONUCLEIC-ACID IN THE RAT},
      journal = {ENDOCRINOLOGY},
      publisher = {ENDOCRINE SOC},
      year = {1993},
      volume = {133},
      number = {6},
      pages = {2561-2567}
    }
    
    BURNS, L., ROBBINS, T. & EVERITT, B. DIFFERENTIAL-EFFECTS OF EXCITOTOXIC LESIONS OF THE BASOLATERAL AMYGDALA, VENTRAL SUBICULUM AND MEDIAL PREFRONTAL CORTEX ON RESPONDING WITH CONDITIONED REINFORCEMENT AND LOCOMOTOR-ACTIVITY POTENTIATED BY INTRAACCUMBENS INFUSIONS OF D-AMPHETAMINE {1993} BEHAVIOURAL BRAIN RESEARCH
    Vol. {55}({2}), pp. {167-183} 
    article  
    Abstract: The experiments reported here have investigated the impact on reward-related processes of lesioning the basolateral amygdala, ventral subiculum and prelimbic cortex which represent the major limbic sources of afferents to the ventral striatum. The results showed that, while lesions of the prelimbic cortex were without effect on the approach to a CS predictive of sucrose reinforcement and the acquisition of a new response with conditioned reinforcement, lesions of the other two structures significantly impaired both responses. However, there were important differences between the effects of basolateral amygdala and ventral subiculum lesions. Thus, lesions of the ventral subiculum completely abolished the locomotor response to intra-accumbens infusions Of D-amphetamine, in addition to blocking the potentiative effect of the same treatment on responding with conditioned reinforcement. Lesions of the basolateral amygdala, by contrast, reduced the control over behaviour by a conditioned reinforcer, but not the potentiation of that control by intra-accumbens D-amphetamine except at the highest dose. Moreover, the locomotor response to D-amphetamine-induced increases in dopamine in the nucleus accumbens was unaffected by amygdala lesions over the dose range blocked by ventral subiculum lesions. The results suggest a rather selective effect of amygdala-ventral striatal interactions on processes subserving conditioned reinforcement and a more fundamental influence of ventral subiculum-ventral striatal interactions in mediating the psychomotor stimulant effects Of D-amphetamine.
    BibTeX:
    @article{BURNS1993,
      author = {BURNS, LH and ROBBINS, TW and EVERITT, BJ},
      title = {DIFFERENTIAL-EFFECTS OF EXCITOTOXIC LESIONS OF THE BASOLATERAL AMYGDALA, VENTRAL SUBICULUM AND MEDIAL PREFRONTAL CORTEX ON RESPONDING WITH CONDITIONED REINFORCEMENT AND LOCOMOTOR-ACTIVITY POTENTIATED BY INTRAACCUMBENS INFUSIONS OF D-AMPHETAMINE},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1993},
      volume = {55},
      number = {2},
      pages = {167-183}
    }
    
    CADOR, M., ROBBINS, T. & EVERITT, B. INVOLVEMENT OF THE AMYGDALA IN STIMULUS REWARD ASSOCIATIONS - INTERACTION WITH THE VENTRAL STRIATUM {1989} NEUROSCIENCE
    Vol. {30}({1}), pp. {77-86} 
    article  
    BibTeX:
    @article{CADOR1989,
      author = {CADOR, M and ROBBINS, TW and EVERITT, BJ},
      title = {INVOLVEMENT OF THE AMYGDALA IN STIMULUS REWARD ASSOCIATIONS - INTERACTION WITH THE VENTRAL STRIATUM},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1989},
      volume = {30},
      number = {1},
      pages = {77-86}
    }
    
    CAHILL, L., BABINSKY, R., MARKOWITSCH, H. & MCGAUGH, J. THE AMYGDALA AND EMOTIONAL MEMORY {1995} NATURE
    Vol. {377}({6547}), pp. {295-296} 
    article  
    BibTeX:
    @article{CAHILL1995,
      author = {CAHILL, L and BABINSKY, R and MARKOWITSCH, HJ and MCGAUGH, JL},
      title = {THE AMYGDALA AND EMOTIONAL MEMORY},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1995},
      volume = {377},
      number = {6547},
      pages = {295-296}
    }
    
    Cahill, L., Haier, R., Fallon, J., Alkire, M., Tang, C., Keator, D., Wu, J. & McGaugh, J. Amygdala activity at encoding correlated with long-term, free recall of emotional information {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({15}), pp. {8016-8021} 
    article  
    Abstract: Positron emission tomography of cerebral glucose metabolism in adult human subjects was used to investigate amygdaloid complex (AC) activity associated with the storage of long-term memory for emotionally arousing events. Subjects viewed two videos (one in each of two separate positron emission tomography sessions, separated by 3-7 days) consisting either of 12 emotionally arousing film clips (''E'' film session) or of 12 relatively emotionally neutral film clips (''N'' film session), and rated their emotional reaction to each film clip immediately after viewing it, Three weeks after the second session, memory for the videos was assessed in a free recall test, As expected, the subjects' average emotional reaction to the E films was higher than that for the N films. In addition, the subjects recalled significantly more E films than N films. Glucose metabolic rate of the right AC while viewing the E films was highly correlated with the number of E films recalled. AC activity was not significantly correlated with the number of N films recalled, The findings support the view derived from both animal and human investigations that the AC is selectively involved with the formation of enhanced long-term memory associated with emotionally arousing events.
    BibTeX:
    @article{Cahill1996,
      author = {Cahill, L and Haier, RJ and Fallon, J and Alkire, MT and Tang, C and Keator, D and Wu, J and McGaugh, JL},
      title = {Amygdala activity at encoding correlated with long-term, free recall of emotional information},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1996},
      volume = {93},
      number = {15},
      pages = {8016-8021}
    }
    
    Cahill, L. & McGaugh, J. Mechanisms of emotional arousal and lasting declarative memory {1998} TRENDS IN NEUROSCIENCES
    Vol. {21}({7}), pp. {294-299} 
    article  
    Abstract: Neuroscience is witnessing growing interest in understanding brain mechanisms of memory formation for emotionally arousing events, a development closely related to renewed interest in the concept of memory consolidation. Extensive research in animals implicates stress hormones and the amygdaloid complex as key,interacting modulators of memory consolidation for emotional events. Considerable evidence suggests that the amygdala is not a site of long-term explicit or declarative memory storage, but serves to influence memory-storage processes in other brain regions, such as the hippocampus, striatum and neocortex. Human-subject studies confirm the prediction of animal work that the amygdala is involved with the formation of enhanced declarative memory for emotionally arousing events.
    BibTeX:
    @article{Cahill1998,
      author = {Cahill, L and McGaugh, JL},
      title = {Mechanisms of emotional arousal and lasting declarative memory},
      journal = {TRENDS IN NEUROSCIENCES},
      publisher = {ELSEVIER SCI LTD},
      year = {1998},
      volume = {21},
      number = {7},
      pages = {294-299}
    }
    
    Calder, A., Keane, J., Manes, F., Antoun, N. & Young, A. Impaired recognition and experience of disgust following brain injury {2000} NATURE NEUROSCIENCE
    Vol. {3}({11}), pp. {1077-1078} 
    article  
    BibTeX:
    @article{Calder2000,
      author = {Calder, AJ and Keane, J and Manes, F and Antoun, N and Young, AW},
      title = {Impaired recognition and experience of disgust following brain injury},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {2000},
      volume = {3},
      number = {11},
      pages = {1077-1078}
    }
    
    Calder, A., Lawrence, A. & Young, A. Neuropsychology of fear and loathing {2001} NATURE REVIEWS NEUROSCIENCE
    Vol. {2}({5}), pp. {352-363} 
    article  
    Abstract: For over 60 years, ideas about emotion in neuroscience and psychology have been dominated by a debate on whether emotion can be encompassed within a single. unifying model. In neuroscience, this approach is epitomized by the limbic system theory and, in psychology, by dimensional models of emotion. Comparative research has gradually eroded the limbic model, and some scientists have proposed that certain individual emotions are represented separately in the brain. Evidence from humans consistent with this approach has recently been obtained by studies indicating that signals of fear and disgust are processed by distinct neural substrates. We review this research and its implications for theories of emotion.
    BibTeX:
    @article{Calder2001,
      author = {Calder, AJ and Lawrence, AD and Young, AW},
      title = {Neuropsychology of fear and loathing},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2001},
      volume = {2},
      number = {5},
      pages = {352-363}
    }
    
    Calder, A., Young, A., Rowland, D., Perrett, D., Hodges, J. & Etcoff, N. Facial emotion recognition after bilateral amygdala damage: Differentially severe impairment of fear {1996} COGNITIVE NEUROPSYCHOLOGY
    Vol. {13}({5}), pp. {699-745} 
    article  
    Abstract: Although the amygdala is widely believed to have a role in the recognition of emotion, a central issue concerns whether it is involved in the recognition of all emotions or whether it is more important to some emotions than to others. We describe studies of two people, DR and SE, with impaired recognition of facial expressions in the context of bilateral amygdala damage. When tested with photographs showing facial expressions of emotion from the Ekman and Friesen (1976) series, both DR and SE showed deficits in the recognition of fear. Problems in recognising fear were also found using photographic quality images interpolated (''morphed'') between prototypes of the six emotions in the Ekman and Friesen (1976) series to create a hexagonal continuum (running from happiness to surprise to fear to sadness to disgust to anger to happiness). Control subjects identified these morphed images as belonging to distinct regions of the continuum, corresponding to the nearest prototype expression. However, DR and SE were impaired on this task, with problems again being most clearly apparent in the region of the fear prototype, An equivalent test of recognition of morphed identities of six famous faces was performed normally by DR, confirming the dissociability of impairments affecting the recognition of identity and expression from the face. Further two-way forced-choice tests showed that DR was unable to tell fear from anger, but could tell happiness from sadness without difficulty. The finding that the recognition of fear can be differentially severely affected by brain injury is consistent with reports of the effects of bilateral amygdala damage in another case (Adolphs, Tranel, Damasio, & Damasio, 1994, 1995). The recognition of facial expressions of basic emotions may therefore be linked, to some extent, to specific neural substrates.
    BibTeX:
    @article{Calder1996,
      author = {Calder, AJ and Young, AW and Rowland, D and Perrett, DI and Hodges, JR and Etcoff, NL},
      title = {Facial emotion recognition after bilateral amygdala damage: Differentially severe impairment of fear},
      journal = {COGNITIVE NEUROPSYCHOLOGY},
      publisher = {PSYCHOLOGY PRESS},
      year = {1996},
      volume = {13},
      number = {5},
      pages = {699-745}
    }
    
    Caldji, C., Francis, D., Sharma, S., Plotsky, P. & Meaney, M. The effects of early rearing environment on the development of GABA(A) and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat {2000} NEUROPSYCHOPHARMACOLOGY
    Vol. {22}({3}), pp. {219-229} 
    article  
    Abstract: We compared the effects of handling or maternal separation from the day following birth until postnatal day 14 on behavioral responses to novelty and on GABA(A) and central benzodiazepine (CBZ) receptor levels in the rat. As adults, handled animals showed reduced startle responsivity, increased exploration in a novel open field, and decreased novelty-induced suppression of feeding relative to the handled (H) and/or maternal separation (MS) groups. As compared with handled animals, both nonhandled (NH) and MS animals displayed: (1) reduced GABA(A) receptor levels in the locus coeruleus (LC) and the n. tractus solitarius (NTS); (2) reduced CBZ receptor sites in the central and lateral n. of the amygdala, the frontal cortex, and in the LC and NTS; and (3) reduced levels of the mRNA for the gamma 2 subunit of the GABA(A) receptor complex, which confers high affinity BZ binding, in the amygdaloid nucleic as well as the he LC and NTS. Both the amygdala and the ascending nonadrenergic systems have been considered as critical sites for the anxiolytic effects of benzodiazepines. These data suggest that early life events influence the development of the GABA(A) receptor system, thus altering the expression of fearfulness in adulthood. [Neuropsychopharmacology 22:229-229, 2000] (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
    BibTeX:
    @article{Caldji2000,
      author = {Caldji, C and Francis, D and Sharma, S and Plotsky, PM and Meaney, MJ},
      title = {The effects of early rearing environment on the development of GABA(A) and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2000},
      volume = {22},
      number = {3},
      pages = {219-229}
    }
    
    Caldji, C., Tannenbaum, B., Sharma, S., Francis, D., Plotsky, P. & Meaney, M. Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({9}), pp. {5335-5340} 
    article  
    Abstract: The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha(2) adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus, The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to ``program'' behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.
    BibTeX:
    @article{Caldji1998,
      author = {Caldji, C and Tannenbaum, B and Sharma, S and Francis, D and Plotsky, PM and Meaney, MJ},
      title = {Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1998},
      volume = {95},
      number = {9},
      pages = {5335-5340}
    }
    
    Campbell, S., Marriott, M., Nahmias, C. & MacQueen, G. Lower hippocampal volume in patients suffering from depression: A meta-analysis {2004} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {161}({4}), pp. {598-607} 
    article  
    Abstract: Objective: A number of studies have used magnetic resonance imaging to examine volumetric differences in temporal structures in subjects suffering from major depressive disorder. Studies have reported lower hippocampal and amygdala volume, but results have been inconsistent. The authors were interested, therefore, in examining these studies in the aggregate in order to determine whether hippocampal volume is lower in major depressive disorder. They also examined factors that may contribute to the disparate results in the literature. Method: A meta-analysis was conducted of studies that used magnetic resonance imaging to assess the volume of the hippocampus and related structures in patients with major depressive disorder. Results: Patients were seen to have lower hippocampal volume relative to comparison subjects, detectable if the hippocampus was measured as a discrete structure. Conclusions: Although the effect of major depressive disorder on amygdala volume remains to be conclusively established, inclusion of the amygdala with the hippocampus appears to have decreased the likelihood of detecting volumetric differences in either structure. Slice thickness or other scan parameters did not account for a substantive amount of the variance in results, whereas clinical variables of the populations studied, such as duration of illness or presence of abuse, may account for much of the discrepancy between findings.
    BibTeX:
    @article{Campbell2004,
      author = {Campbell, S and Marriott, M and Nahmias, C and MacQueen, GM},
      title = {Lower hippocampal volume in patients suffering from depression: A meta-analysis},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      publisher = {AMER PSYCHIATRIC PRESS, INC},
      year = {2004},
      volume = {161},
      number = {4},
      pages = {598-607}
    }
    
    CAMPEAU, S. & DAVIS, M. INVOLVEMENT OF THE CENTRAL NUCLEUS AND BASOLATERAL COMPLEX OF THE AMYGDALA IN FEAR CONDITIONING MEASURED WITH FEAR-POTENTIATED STARTLE IN RATS TRAINED CONCURRENTLY WITH AUDITORY AND VISUAL CONDITIONED-STIMULI {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({3, Part 2}), pp. {2301-2311} 
    article  
    Abstract: The goal of this work was to test the involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning, using auditory and visual conditioned stimuli (CSs). The acoustic startle reflex in rats was used as the behavioral index of conditioning because startle is reliably enhanced in the presence of a conditioned stimulus (CS) previously paired with a footshock. Initially, differential conditioning procedures indicated reliable discrimination between a noise CS and a visual CS. Subsequently, the effects of amygdala lesions were evaluated when both modalities were paired with shocks in the same rats. Electrolytic or ibotenic acid lesions of the central nucleus of the amygdala blocked fear-potentiated startle to both auditory and visual CSs, consistent with the idea that the central nucleus serves as a response independent, final common relay for fear conditioning. Similarly, pre- or posttraining electrolytic or NMDA-induced lesions of the basolateral complex of the amygdala, which damaged the lateral nucleus, and most of the basolateral nucleus, disrupted fear-potentiated startle to both CS modalities. This finding is consistent with the suggestion that, in fear conditioning, the basolateral complex of the amygdala serves as an obligatory relay of sensory information from subcortical and cortical sensory areas to the central nucleus of the amygdala.
    BibTeX:
    @article{CAMPEAU1995,
      author = {CAMPEAU, S and DAVIS, M},
      title = {INVOLVEMENT OF THE CENTRAL NUCLEUS AND BASOLATERAL COMPLEX OF THE AMYGDALA IN FEAR CONDITIONING MEASURED WITH FEAR-POTENTIATED STARTLE IN RATS TRAINED CONCURRENTLY WITH AUDITORY AND VISUAL CONDITIONED-STIMULI},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1995},
      volume = {15},
      number = {3, Part 2},
      pages = {2301-2311}
    }
    
    CANTERAS, N., SIMERLY, R. & SWANSON, L. ORGANIZATION OF PROJECTIONS FROM THE MEDIAL NUCLEUS OF THE AMYGDALA - A PHAL STUDY IN THE RAT {1995} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {360}({2}), pp. {213-245} 
    article  
    Abstract: The organization of axonal projections from the four recognized parts of the medial amygdalar nucleus (MEA) were characterized with the Phaesolus vulgaris leucoagglutinin (PHAL) method in male rats. The results indicate that the MEA consists of two major divisions, ventral and dorsal, and that the former may also consist of rostral and caudal regions. As a whole, the MEA generates centrifugal projections to several parts of the accessory and main olfactory sensory pathways, and projections to a) several parts of the intrahippocampal circuit (ventrally); b) the ventral striatum, ventral pallidum, and bed nuclei of the stria terminalis (BST) in the basal telencephaon; c) many parts of the hypothalamus; d) midline and medial parts of the thalamus; and e) the periaqueductal gray, ventral tegmental area, and midbrain raphe. The dorsal division of the MEA (the posterodorsal part) is characterized by projections to the principal nucleus of the BST, and to the anteroventral periventricular, medial, and central parts of the medial preoptic, and ventral premammillary hypothalamic nuclei. These hypothalamic nuclei project heavily to neuroendocrine and autonomic-related parts of the hypothalamic periventricular zone. The ventral division of the MEA (the anterodorsal, anteroventral, and posteroventral parts) is characterized by dense projections to the transverse and interfascicular nuclei of the BST, and to the lateral part of the medial preoptic, anterior hypothalamic, and ventromedial hypothalamic nuclei. However, dorsal regions of the ventral division provide rather dense inputs to the medial preoptic region and capsule of the ventromedial nucleus, whereas ventral regions of the ventral division preferentially innervate the anterior hypothalamic, dorsomedial, and ventral parts of the ventromedial nuclei. Functional evidence suggests that circuits associated with dorsal regions of the ventral division may deal with reproductive behavior, whereas circuits associated with ventral regions of the ventral division may deal preferentially with agonistic behavior. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{CANTERAS1995,
      author = {CANTERAS, NS and SIMERLY, RB and SWANSON, LW},
      title = {ORGANIZATION OF PROJECTIONS FROM THE MEDIAL NUCLEUS OF THE AMYGDALA - A PHAL STUDY IN THE RAT},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1995},
      volume = {360},
      number = {2},
      pages = {213-245}
    }
    
    CANTERAS, N., SIMERLY, R. & SWANSON, L. ORGANIZATION OF PROJECTIONS FROM THE VENTROMEDIAL NUCLEUS OF THE HYPOTHALAMUS - A PHASEOLUS-VULGARIS-LEUKOAGGLUTININ STUDY IN THE RAT {1994} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {348}({1}), pp. {41-79} 
    article  
    Abstract: The organization of projections from the four parts of the ventromedial nucleus (VMH) and a ventrolaterally adjacent region tentatively identified as the tuberal nucleus (TU) have been analyzed with small injections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Extrinsic and intranuclear projections of each part of the VMH display clear quantitative differences, whereas the overall patterns of outputs are qualitatively similar. Overall, the VMH establishes massive intrahypothalamic terminal fields in other parts of the medial zone, tending to avoid the periventricular and lateral zones. The ventrolateral VMH is more closely related to other parts of the hypothalamus that also express gonadal steroid hormone receptors, including the medial preoptic, tuberal, and ventral premamillary nuclei, whereas other parts of the VMH are more closely related to the anterior hypothalamic and dorsal premammillary nuclei. All parts of the VMH project to the zona incerta (including the A13 region) and parts of the midline thalamus, including the paraventricular and parataenial nuclei and nucleus reuniens. The densest inputs to the septum are to the bed nuclei of the stria terminalis, where the ventrolateral and central VMH innervate the anteroventral and anterodorsal areas and transverse and interfascicular nuclei, whereas the anterior and dorsomedial VMH innervate the latter two. The central, lateral, and medial amygdalar nuclei receive substantial inputs from various parts of the VMH. Other regions of the telencephalon, including the nucleus accumbens and the piriform-amygdaloid, infralimbic, prelimbic, anterior cingulate, agranular insular, piriform, perirhinal, entorhinal, and postpiriform transition areas, also receive sparse inputs. All parts of the VMH send a massive, topographically organized projection to the periaqueductal gray. Other brainstem terminal fields include the superior colliculus, peripeduncular area, locus coeruleus, Barrington's nucleus, parabrachial nucleus, nucleus of the solitary tract, and the mesencephalic, pontine, gigantocellular, paragigantocellular, and parvicellular reticular nuclei. The projections of the TU are similar to, and a subset of, those from the VMH and are thus not nearly as widespread as those from adjacent parts of the lateral hypothalamic area. Because of these similarities, the TU may eventually come to be viewed most appropriately as the lateral component of the VMH itself. The functional implications of the present findings are discussed in view of evidence that the VMH plays a role in the expression of ingestive, affective, and copulatory behaviors. (C) 1994 Wiley-Liss, Inc.
    BibTeX:
    @article{CANTERAS1994,
      author = {CANTERAS, NS and SIMERLY, RB and SWANSON, LW},
      title = {ORGANIZATION OF PROJECTIONS FROM THE VENTROMEDIAL NUCLEUS OF THE HYPOTHALAMUS - A PHASEOLUS-VULGARIS-LEUKOAGGLUTININ STUDY IN THE RAT},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1994},
      volume = {348},
      number = {1},
      pages = {41-79}
    }
    
    CANTERAS, N. & SWANSON, L. PROJECTIONS OF THE VENTRAL SUBICULUM TO THE AMYGDALA, SEPTUM, AND HYPOTHALAMUS - A PHAL ANTEROGRADE TRACT-TRACING STUDY IN THE RAT {1992} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {324}({2}), pp. {180-194} 
    article  
    Abstract: The projections of the ventral subiculum are organized differentially along the dorsoventral (or septotemporal) axis of this cortical field, with more ventral regions playing a particularly important role in hippocampal communication with the amygdala, bed nuclei of the stria terminalis (BST), and rostral hypothalamus. In the present study we re-examined the projection of the ventral subiculum to these regions with the Phaseolus vulgaris leucoagglutinin (PHAL) method in the rat. The results confirm and extend earlier conclusions based primarily on the autoradiographic method, Projections from the ventral subiculum course either obliquely through the angular bundle to innervate the amygdala and adjacent parts of the temporal lobe, or follow the alveus and fimbria to the precommissural fornix and medial corticohypothalamic tract. The major amygdalar terminal field is centered in the posterior basomedial nucleus, while other structures that appear to be innervated include the piriform-amygdaloid area, the posterior basolateral, posterior cortical, posterior, central, medial, and intercalated nuclei, and the nucleus of the lateral olfactory tract. Projections from the ventral subiculum reach the BST mainly by way of the precommissural fornix, and provide rather dense inputs to the anterodorsal area as well as the transverse and interfascicular nuclei. The medial corticohypothalamic tract is the main route taken by fibers from the ventral subiculum to the hypothalamus, where they innervate the medial preoptic area, ``shell'' of the ventromedial nucleus, dorsomedial nucleus, ventral premammillary nucleus, and cell-poor zone around the medial mammillary nucleus. We also observed a rather dense terminal field just dorsal to the suprachiasmatic nucleus that extends dorsally and caudally to fill the subparaventricular zone along the medial border of the anterior hypothalamic nucleus and ventrolateral border of the paraventricular nucleus. The general pattern of outputs to the hypothalamus and septum is strikingly similar for the ventral subiculum and suprachiasmatic nucleus, the endogenous circadian rhythm generator.
    BibTeX:
    @article{CANTERAS1992,
      author = {CANTERAS, NS and SWANSON, LW},
      title = {PROJECTIONS OF THE VENTRAL SUBICULUM TO THE AMYGDALA, SEPTUM, AND HYPOTHALAMUS - A PHAL ANTEROGRADE TRACT-TRACING STUDY IN THE RAT},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1992},
      volume = {324},
      number = {2},
      pages = {180-194}
    }
    
    Cardinal, R., Parkinson, J., Hall, J. & Everitt, B. Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex {2002} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {26}({3}), pp. {321-352} 
    article  
    Abstract: Emotions are multifaceted, but a key aspect of emotion involves the assessment of the value of environmental stimuli. This article reviews the many psychological representations, including representations of stimulus value, which are formed in the brain during Pavlovian and instrumental conditioning tasks. These representations may be related directly to the functions of cortical and subcortical neural structures. The basolateral amygdala (BLA) appears to be required for a Pavlovian conditioned stimulus (CS) to gain access to the current value of the specific unconditioned stimulus (US) that it predicts, while the central nucleus of the amygdala acts as a controller of brainstem arousal and response systems, and subserves some forms of stimulus-response Pavlovian conditioning. The nucleus accumbens, which appears not to be required for knowledge of the contingency between instrumental actions and their outcomes, nevertheless influences instrumental behaviour strongly by allowing Pavlovian CSs to affect the level of instrumental responding (Pavlovian-instrumental transfer), and is required for the normal ability of animals to choose rewards that are delayed. The prelimbic cortex is required for the detection of instrumental action-outcome contingencies, while insular cortex may allow rats to retrieve the values of specific foods via their sensory properties. The orbitofrontal cortex, like the BLA, may represent aspects of reinforcer value that govern instrumental choice behaviour. Finally, the anterior cingulate cortex, implicated in human disorders of emotion and attention, may have multiple roles in responding to the emotional significance of stimuli and to errors in performance, preventing responding to inappropriate stimuli. (C) 2002 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Cardinal2002,
      author = {Cardinal, RN and Parkinson, JA and Hall, J and Everitt, BJ},
      title = {Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2002},
      volume = {26},
      number = {3},
      pages = {321-352}
    }
    
    Carmichael, S. & Price, J. Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys {1995} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {363}({4}), pp. {615-641} 
    article  
    Abstract: Previous studies have shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures. In this study, the organization of these projections was defined in relation to architectonic areas within the OMPFC. All of the limbic structures were substantially connected with the following posterior and medial orbital areas: the posteromedial, medial, intermediate, and lateral agranular insular areas (Iapm, Iam, Iai, and Ial, respectively) and areas 11m, 13a, 13b, 14c, and 14r. In contrast, lateral orbital areas 12o, 12m, and 12l and medial wall areas 24a,b and 32 were primarily connected with the amygdala, the temporal pole, and the cingulate cortex. Data were not obtained on the posteroventral medial wall. Three distinct projections were recognized from the basal amygdaloid nucleus: 1) The dorsal part projected to area 121; 2) the ventromedial part projected to most areas in the posterior and medial orbital cortex except for areas Iai, 12o, 13a, and 14c; and 3) the ventrolateral part projected to orbital areas 120, Iai, 13a, 14c, and to the medial wall areas. The accessory basal and lateral amygdaloid nuclei projected most strongly to areas in the posterior and medial orbital cortex. The medial, anterior cortical, and central amygdaloid nuclei and the periamygdaloid cortex were connected with the posterior orbital areas. The projection from the hippocampus originated from the rostral subiculum and terminated in the medial orbital areas. The same region was reciprocally connected with the anteromedial nucleus of the thalamus, which received input from the rostral subiculum. The parahippocampal cortical areas (including the temporal polar, entorhinal, perirhinal, and posterior parahippocampal cortices) were primarily connected with posterior and medial orbital areas, with some projections to the dorsal part of the medial wall. The rostral cingulate cortex sent fibers to the medial wall, to the medial orbital areas, and to lateral areas 12o, 12r, and Iai. The posterior cingulate gyrus, including the caudomedial lobule, was especially strongly connected with area 11m. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{Carmichael1995,
      author = {Carmichael, ST and Price, JL},
      title = {Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1995},
      volume = {363},
      number = {4},
      pages = {615-641}
    }
    
    Carr, L., Iacoboni, M., Dubeau, M., Mazziotta, J. & Lenzi, G. Neural mechanisms of empathy in humans: A relay from neural systems for imitation to limbic areas {2003} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {100}({9}), pp. {5497-5502} 
    article DOI  
    Abstract: How do we empathize with others? A mechanism according to which action representation modulates emotional activity may provide an essential functional architecture for empathy. The superior temporal and inferior frontal cortices are critical areas for action representation and are connected to the limbic system via the insula. Thus, the insula may be a critical relay from action representation to emotion. We used functional Mill while subjects were either imitating or simply observing emotional facial expressions. Imitation and observation of emotions activated a largely similar network of brain areas. Within this network, there was greater activity during imitation, compared with observation of emotions, in premotor areas including the inferior frontal cortex, as well as in the superior temporal cortex, insula, and amygdala. We understand what others feel by a mechanism of action representation that allows empathy and modulates our emotional content. The insula plays a fundamental role in this mechanism.
    BibTeX:
    @article{Carr2003,
      author = {Carr, L and Iacoboni, M and Dubeau, MC and Mazziotta, JC and Lenzi, GL},
      title = {Neural mechanisms of empathy in humans: A relay from neural systems for imitation to limbic areas},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {2003},
      volume = {100},
      number = {9},
      pages = {5497-5502},
      doi = {{10.1073/pnas.0935845100}}
    }
    
    Carrasco, G. & de Kar, L. Neuroendocrine pharmacology of stress {2003} EUROPEAN JOURNAL OF PHARMACOLOGY
    Vol. {463}({1-3}), pp. {235-272} 
    article DOI  
    Abstract: Exposure to hostile conditions initiates responses organized to enhance the probability of survival. These coordinated responses, known as stress responses, are composed of alterations in behavior, autonomic function and the secretion of multiple hormones. The activation of the renin-angiotensin system and the hypothalamic-pituitary-adrenocortical axis plays a pivotal role in the stress response. Neuroendocrine components activated by stressors include the increased secretion of epinephrine and norepinephrine from the sympathetic nervous system and adrenal medulla, the release of corticotropin-releasing factor (CRF) and vasopressin from parvicellular neurons into the portal circulation, and seconds later, the secretion of pituitary adrenocorticotropin (ACTH), leading to secretion of glucocorticoids by the adrenal gland. Corticotropin-releasing factor coordinates the endocrine, autonomic, behavioral and immune responses to stress and also acts as a neurotransmitter or neuromodulator in the amygdala, dorsal raphe nucleus, hippocampus and locus coeruleus, to integrate brain multi-system responses to stress. This review discussed the role of classical mediators of the stress response, such as corticotropin-releasing factor, vasopressin, serotonin (5-hydroxytryptamine or 5-HT) and catecholamines. Also discussed are the roles of other neuropeptides/neuromodulators involved in the stress response that have previously received little attention, such as substance P, vasoactive intestinal polypeptide, neuropeptide Y and cholecystokinin. Anxiolytic drugs of the benzodiazepine class and other drugs that affect catecholamine, GABA(A), histamine and serotonin receptors have been used to attenuate the neuroendocrine response to stressors. The neuroendocrine information for these drugs is still incomplete; however, they are a new class of potential antidepressant and anxiolytic drugs that offer new therapeutic approaches to treating anxiety disorders. The studies described in this review suggest that multiple brain mechanisms are responsible for the regulation of each hormone and that not all hormones are regulated by the same neural circuits. In particular, the renin-angiotensin system seems to be regulated by different brain mechanisms than the hypothalamic-pituitary-adrenal system. This could be an important survival mechanism to ensure that dysfunction of one neurotransmitter system will not endanger the appropriate secretion of hormones during exposure to adverse conditions. The measurement of several hormones to examine the mechanisms underlying the stress response and the effects of drugs and lesions on these responses can provide insight into the nature and location of brain circuits and neurotransmitter receptors involved in anxiety and stress. (C) 2003 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Carrasco2003,
      author = {Carrasco, GA and de Kar, LDV},
      title = {Neuroendocrine pharmacology of stress},
      journal = {EUROPEAN JOURNAL OF PHARMACOLOGY},
      publisher = {ELSEVIER SCIENCE BV},
      year = {2003},
      volume = {463},
      number = {1-3},
      pages = {235-272},
      doi = {{10.1016/S0014-2999(03)01285-8}}
    }
    
    Castellanos, F., Giedd, J., Marsh, W., Hamburger, S., Vaituzis, A., Dickstein, D., Sarfatti, S., Vauss, Y., Snell, J., Lange, N., Kaysen, D., Krain, A., Ritchie, G., Rajapakse, J. & Rapoport, J. Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder {1996} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {53}({7}), pp. {607-616} 
    article  
    Abstract: Background: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. Method: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. Conclusion: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.
    BibTeX:
    @article{Castellanos1996,
      author = {Castellanos, FX and Giedd, JN and Marsh, WL and Hamburger, SD and Vaituzis, AC and Dickstein, DP and Sarfatti, SE and Vauss, YC and Snell, JW and Lange, N and Kaysen, D and Krain, AL and Ritchie, GF and Rajapakse, JC and Rapoport, JL},
      title = {Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      publisher = {AMER MEDICAL ASSOC},
      year = {1996},
      volume = {53},
      number = {7},
      pages = {607-616}
    }
    
    Castelli, F., Frith, C., Happe, F. & Frith, U. Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes {2002} BRAIN
    Vol. {125}({Part 8}), pp. {1839-1849} 
    article  
    Abstract: Ten able adults with autism or Asperger syndrome and 10 normal volunteers were PET scanned while watching animated sequences. The animations depicted two triangles moving about on a screen in three different conditions: moving randomly, moving in a goal-directed fashion (chasing, fighting), and moving interactively with implied intentions (coaxing, tricking). The, last condition frequently elicited descriptions in terms of mental states that viewers attributed to the triangles (mentalizing). The autism group gave fewer and less accurate descriptions of these latter animations, but equally accurate descriptions of the other animations compared with controls. While viewing animations that elicited mentalizing, in contrast to randomly moving shapes, the normal group showed increased activation in a previously identified mentalizing network (medial prefrontal cortex, superior temporal sulcus at the temporoparietal junction and temporal poles). The autism group showed less activation than the normal group in all these regions. However, one additional region, extrastriate cortex, which was highly active when watching animations that elicited mentalizing, showed the same amount of increased activation in both groups. In the autism group this extrastriate region showed reduced functional connectivity with the superior temporal sulcus at the temporo-parietal junction, an area associated with the processing of biological motion as well as with mentalizing. This finding suggests a physiological cause for the mentalizing dysfunction in autism: a bottleneck in the interaction between higher order and lower order perceptual processes.
    BibTeX:
    @article{Castelli2002,
      author = {Castelli, Fulvia and Frith, Chris and Happe, Francesca and Frith, Uta},
      title = {Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {2002},
      volume = {125},
      number = {Part 8},
      pages = {1839-1849}
    }
    
    Castelli, F., Happe, F., Frith, U. & Frith, C. Movement and mind: A functional imaging study of perception and interpretation of complex intentional movement patterns {2000} NEUROIMAGE
    Vol. {12}({3}), pp. {314-325} 
    article DOI  
    Abstract: We report a functional neuroimaging study with positron emission tomography (PET) in which six healthy adult volunteers were scanned while watching silent computer-presented animations. The characters in the animations were simple geometrical shapes whose movement patterns selectively evoked mental state attribution or simple action description. Results showed increased activation in association with mental state attribution in four main regions: medial prefrontal cortex, temporoparietal junction (superior temporal sulcus), basal temporal regions (fusiform gyrus and temporal poles adjacent to the amygdala), and extrastriate cortex (occipital gyrus). Previous imaging studies have implicated these regions in self-monitoring, in the perception of biological motion, and in the attribution of mental states using verbal stimuli or visual depictions of the human form. Ne suggest that these regions form a network for processing information about intentions, and speculate that the ability to make inferences about other people's mental states evolved from the ability to make inferences about other creatures' actions. (C) 2000 Academic Press.
    BibTeX:
    @article{Castelli2000,
      author = {Castelli, F and Happe, F and Frith, U and Frith, C},
      title = {Movement and mind: A functional imaging study of perception and interpretation of complex intentional movement patterns},
      journal = {NEUROIMAGE},
      publisher = {ACADEMIC PRESS INC},
      year = {2000},
      volume = {12},
      number = {3},
      pages = {314-325},
      doi = {{10.1006/nimg.2000.0612}}
    }
    
    Cavada, C., Company, T., Tejedor, J., Cruz-Rizzolo, R. & Reinoso-Suarez, F. The anatomical connections of the macaque monkey orbitofrontal cortex. A review {2000} CEREBRAL CORTEX
    Vol. {10}({3}), pp. {220-242} 
    article  
    Abstract: The orbitofrontal cortex (OfC) is a heterogeneous prefrontal sector selectively connected with a wide constellation of other prefrontal. limbic, sensory and promotor areas. Among the limbic cortical connections, the ones with the hippocampus and parahippocampal cortex are particularly salient. Sensory cortices connected with the OfC include areas involved in olfactory, gustatory, somatosensory, auditory and visual processing. Subcortical structures with prominent OfC connections include the amygdala. numerous thalamic nuclei. the striatum, hypothalamus. periaqueductal gray matter, and biochemically specific cell groups in the basal forebrain and brainstem. Architectonic and connectional evidence supports parcellation of the OfC. The rostrally placed isocortical sector is mainly connected with isocortical areas, including sensory areas of the auditory, somatic and visual modalities, whereas the caudal non-isocortical sector is principally connected with non-isocortical areas, and, in the sensory domain, with olfactory and gustatory areas. The connections of the isocortical and non-isocortical orbital sectors with the amygdala, thalamus, striatum, hypothalamus and periaqueductal gray matter are also specific. The medial sector of the OfC is selectively connected with the hippocampus. posterior parahippocampal cortex, posterior cingulate and retrosplenial areas, and area prostriata, while the lateral orbitofrontal sector is the most heavily connected with sensory areas of the gustatory, somatic and visual modalities, with premotor regions, and with the amygdala.
    BibTeX:
    @article{Cavada2000,
      author = {Cavada, C and Company, T and Tejedor, J and Cruz-Rizzolo, RJ and Reinoso-Suarez, F},
      title = {The anatomical connections of the macaque monkey orbitofrontal cortex. A review},
      journal = {CEREBRAL CORTEX},
      publisher = {OXFORD UNIV PRESS INC},
      year = {2000},
      volume = {10},
      number = {3},
      pages = {220-242}
    }
    
    CAVAZOS, J., GOLARAI, G. & SUTULA, T. MOSSY FIBER SYNAPTIC REORGANIZATION INDUCED BY KINDLING - TIME COURSE OF DEVELOPMENT, PROGRESSION, AND PERMANENCE {1991} JOURNAL OF NEUROSCIENCE
    Vol. {11}({9}), pp. {2795-2803} 
    article  
    Abstract: Recent studies have revealed that mossy fiber axons of granule cells in the dentate gyrus undergo reorganization of their terminal projections in both animal models of epilepsy and human epilepsy. This synaptic reorganization has been demonstrated by the Timm method, a histochemical technique that selectively labels synaptic terminals of mossy fibers because of their high zinc content. It has been generally presumed that the reorganization of the terminal projections of the mossy fiber pathway is a consequence of axonal sprouting and synaptogenesis by mossy fibers. To evaluate this possibility further, the time course for development of Timm granules, which correspond ultrastructurally to mossy fiber synaptic terminals, was examined in the supragranular layer of the dentate gyrus at the initiation of kindling stimulation with an improved scoring method for assessment of alterations in Timm histochemistry. The progression and permanence of this histological alteration were similarly evaluated during the behavioral and electrographic evolution of kindling evoked by perforant path, amygdala, or olfactory bulb stimulation. Mossy fiber synaptic terminals developed in the supragranular region of the dentate gyrus by 4 d after initiation of kindling stimulation in a time course compatible with axon sprouting. The induced alterations in the terminal projections of the mossy fiber pathway progressed with the evolution of behavioral kindled seizures, became permanent in parallel with the development of longlasting susceptibility to evoked seizures, and were observed as long as 8 months after the last evoked kindled seizure. The results demonstrated a strong correlation between mossy fiber synaptic reorganization and the development, progression, and permanence of the kindling phenomenon.
    BibTeX:
    @article{CAVAZOS1991,
      author = {CAVAZOS, JE and GOLARAI, G and SUTULA, TP},
      title = {MOSSY FIBER SYNAPTIC REORGANIZATION INDUCED BY KINDLING - TIME COURSE OF DEVELOPMENT, PROGRESSION, AND PERMANENCE},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1991},
      volume = {11},
      number = {9},
      pages = {2795-2803}
    }
    
    Caviness, V., Kennedy, D., Richelme, C., Rademacher, J. & Filipek, P. The human brain age 7-11 years: A volumetric analysis based on magnetic resonance images {1996} CEREBRAL CORTEX
    Vol. {6}({5}), pp. {726-736} 
    article  
    Abstract: Volumetric magnetic resonance image (MRI)-based morphometry was performed on the brains of 30 normal children (15 males and 15 males) with a mean age of 9 years (range 7-11 years). This age range lies in a late hut critical phase of brain growth where net volumetric increment will be small hut when the details of brain circuity are being fine-tuned to support the operations of the adult brain. The brain at this age is 95% the volume of the adult brain. The brain of the female child is 93% the volume of the male child. For more than 95% of brain structures, the volumetric differences in male and female child brain are uniformly scaled to the volume difference of the total brain in the two sexes. Exceptions to this pattern of uniform scaling are the caudate, hippocampus and pallidum, which are disproportionately larger in female than male child brain, and the amygdala, which is disproportionately smaller in the female child brain. The patterns of uniform scaling are generally sustained during the final volumetric increment in overall brain size between age 7-11 and adulthood. There are exceptions to this uniform scaling of child to adult brain, and certain of these exceptions are sexually dimorphic. Thus, with respect to major brain regions, the cerebellum in the female but not the male child is already at adult volume while the brainstem in both sexes must enlarge more than the brain as a whole. The collective subcortical gray matter structures of the forebrain of the female child are already at their adult volumes. The volumes of these same structures in the male child, by contrast, are greater than their adult volumes and, by implication, must regress in volume before adulthood. The volume of the central white matter, on the other hand, is disproportionately smaller in female than male child brain with respect to the adult volumes of cerebral central white matter. By implication, relative volumetric increase of cerebral central white matter by adulthood must be greater in the female than male brain. The juxtaposed progressive and regressive patterns of growth of brain structures implied by these observations in the human brain have a soundly established precedent in the developing rhesus brain. There is emerging evidence that sexually dimorphic abnormal regulation of these terminal patterns of brain development are associated with gravely disabling human disorders of obscure etiology.
    BibTeX:
    @article{Caviness1996,
      author = {Caviness, VS and Kennedy, DN and Richelme, C and Rademacher, J and Filipek, PA},
      title = {The human brain age 7-11 years: A volumetric analysis based on magnetic resonance images},
      journal = {CEREBRAL CORTEX},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1996},
      volume = {6},
      number = {5},
      pages = {726-736}
    }
    
    CENDES, F., ANDERMANN, F., DUBEAU, F., GLOOR, P., EVANS, A., JONESGOTMAN, M., OLIVIER, A., ANDERMANN, E., ROBITAILLE, Y., LOPESCENDES, I., PETERS, T. & MELANSON, D. EARLY-CHILDHOOD PROLONGED FEBRILE CONVULSIONS, ATROPHY AND SCLEROSIS OF MESIAL STRUCTURES, AND TEMPORAL-LOBE EPILEPSY - AN MRI VOLUMETRIC STUDY {1993} NEUROLOGY
    Vol. {43}({6}), pp. {1083-1087} 
    article  
    Abstract: We performed MRI volumetric measurements of the amygdala (AM) and hippocampal formation (HF) in a group of 43 patients with temporal lobe epilepsy not controlled by optimal drug treatment. Fifteen patients (35 had a history of prolonged febrile convulsions (PFC) in early childhood; 30 patients underwent surgery, and histopathology was available in twenty-four. The mean values of AM and HF volumes ipsilateral to the EEG focus were significantly smaller than those of normal controls. The volumetric measurements showed a more pronounced atrophy of the AM in patients with a history of PFC, although the HF volumes were also smaller in this group. Patients with a history of PFC had a higher proportion of more severe mesial temporal sclerosis (MTS) compared with those with no PFC. These findings confirm a correlation between early childhood PFC, the severity of atrophy of mesial structures, and MTS.
    BibTeX:
    @article{CENDES1993,
      author = {CENDES, F and ANDERMANN, F and DUBEAU, F and GLOOR, P and EVANS, A and JONESGOTMAN, M and OLIVIER, A and ANDERMANN, E and ROBITAILLE, Y and LOPESCENDES, I and PETERS, T and MELANSON, D},
      title = {EARLY-CHILDHOOD PROLONGED FEBRILE CONVULSIONS, ATROPHY AND SCLEROSIS OF MESIAL STRUCTURES, AND TEMPORAL-LOBE EPILEPSY - AN MRI VOLUMETRIC STUDY},
      journal = {NEUROLOGY},
      publisher = {LIPPINCOTT-RAVEN PUBL},
      year = {1993},
      volume = {43},
      number = {6},
      pages = {1083-1087}
    }
    
    CENDES, F., ANDERMANN, F., GLOOR, P., EVANS, A., JONESGOTMAN, M., WATSON, C., MELANSON, D., OLIVIER, A., PETERS, T., LOPESCENDES, I. & LEROUX, G. MRI VOLUMETRIC MEASUREMENT OF AMYGDALA AND HIPPOCAMPUS IN TEMPORAL-LOBE EPILEPSY {1993} NEUROLOGY
    Vol. {43}({4}), pp. {719-725} 
    article  
    Abstract: We performed MRI volumetric measurements of the amygdala (AM), the hippocampal formation (HF), and the anterior temporal lobe in a group of 30 patients with intractable temporal lobe epilepsy (TLE) and in seven patients with extratemporal lobe foci. Measurements were analyzed with a semiautomated software program and the results compared with those of normal controls and correlated with the findings of all other investigations. In particular, we compared the results with the lateralization of epileptic abnormalities in the EEG. Volumetric studies of AM and HF showed lateralization of measurable atrophy consistent with that derived from extracranial and intracranial EEG examinations. The HF volumes were more sensitive and provided a lateralization in 87 Combined measurements of AM and HF showed lateralization in 93 always congruent with the results of EEG lateralization. This slight but important additional improvement in discrimination justifies using AM measurements in MRI volumetric studies of mesial temporal structures. Volumetric studies combined with other currently employed noninvasive techniques may diminish the need for invasive methods of investigation in patients with TLE.
    BibTeX:
    @article{CENDES1993a,
      author = {CENDES, F and ANDERMANN, F and GLOOR, P and EVANS, A and JONESGOTMAN, M and WATSON, C and MELANSON, D and OLIVIER, A and PETERS, T and LOPESCENDES, I and LEROUX, G},
      title = {MRI VOLUMETRIC MEASUREMENT OF AMYGDALA AND HIPPOCAMPUS IN TEMPORAL-LOBE EPILEPSY},
      journal = {NEUROLOGY},
      publisher = {LIPPINCOTT-RAVEN PUBL},
      year = {1993},
      volume = {43},
      number = {4},
      pages = {719-725}
    }
    
    Chan, D., Fox, N., Scahill, R., Crum, W., Whitwell, J., Leschziner, G., Rossor, A., Stevens, J., Cipolotti, L. & Rossor, M. Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease {2001} ANNALS OF NEUROLOGY
    Vol. {49}({4}), pp. {433-442} 
    article  
    Abstract: Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia and Alzheimer's disease. Three groups of 10 subjects were studied: semantic dementia patients, Alzheimer's disease patients, and control subjects. The temporal lobe structures measured were the amygdala, hippocampus, entorhinal cortex, parahippocampal gyrus, fusiform gyrus, and superior, middle, and inferior temporal gyri. Semantic dementia and Alzheimer's disease groups did not differ significantly on global atrophy measures. In semantic dementia, there was asymmetrical temporal lobe atrophy, with greater left-sided damage. There was an anteroposterior gradient in the distribution of temporal lobe atrophy, with more marked atrophy anteriorly. All left anterior temporal lobe structures were affected in semantic dementia, with the entorhinal cortex, amygdala, middle and inferior temporal gyri, and fusiform gyrus the most severely damaged. Asymmetrical, predominantly anterior hippocampal atrophy was also present. In Alzheimer's disease, there was symmetrical atrophy of the entorhinal cortex, hippocampus, and amygdala, with no evidence of an anteroposterior gradient in the distribution of temporal Lobe or hippocampal atrophy. These data demonstrate that there is a marked difference in the distribution of temporal lobe atrophy in semantic dementia and Alzheimer's disease. In addition, the pattern of atrophy in semantic dementia suggests that semantic memory is subserved by anterior temporal lobe structures, within which the middle and inferior temporal gyri may play a key role.
    BibTeX:
    @article{Chan2001,
      author = {Chan, D and Fox, NC and Scahill, RI and Crum, WR and Whitwell, JL and Leschziner, G and Rossor, AM and Stevens, JM and Cipolotti, L and Rossor, MN},
      title = {Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease},
      journal = {ANNALS OF NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {2001},
      volume = {49},
      number = {4},
      pages = {433-442}
    }
    
    Childress, A., Mozley, P., McElgin, W., Fitzgerald, J., Reivich, M. & O'Brien, C. Limbic activation during cue-induced cocaine craving {1999} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {156}({1}), pp. {11-18} 
    article  
    Abstract: Objective: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans. Method: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions. Results: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the nondrug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). Conclusions: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.
    BibTeX:
    @article{Childress1999,
      author = {Childress, AR and Mozley, PD and McElgin, W and Fitzgerald, J and Reivich, M and O'Brien, CP},
      title = {Limbic activation during cue-induced cocaine craving},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      publisher = {AMER PSYCHIATRIC PRESS, INC},
      year = {1999},
      volume = {156},
      number = {1},
      pages = {11-18},
      note = {149th Annual Meeting of the American-Psychiatric-Association, NEW YORK, NEW YORK, MAY 04-09, 1996}
    }
    
    CIABARRA, A., SULLIVAN, J., GAHN, L., PECHT, G., HEINEMANN, S. & SEVARINO, K. CLONING AND CHARACTERIZATION OF CHI-1 - A DEVELOPMENTALLY-REGULATED MEMBER OF A NOVEL CLASS OF THE IONOTROPIC GLUTAMATE-RECEPTOR FAMILY {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({10}), pp. {6498-6508} 
    article  
    Abstract: Ionotropic glutamate receptors are composed of homomeric or heteromeric configurations of glutamate receptor subunits. We have cloned a member of a novel class of the rat ionotropic glutamate receptor family, termed chi-1. This subunit exhibits an average identity of 27% to NMDA subunits and 23% to non-NMDA subunits. Regional transcript levels of chi-1 are elevated just prior to and during the first postnatal week, with the highest levels present in the spinal cord, brainstem, hypothalamus, thalamus, CA1 field of the hippocampus, and amygdala. The spatial distribution of chi-1 expression is similar from postnatal day 1 (P1) to adulthood. However, transcript levels decline sharply between P7 and P14 and remain attenuated into adulthood. Functional expression studies in Xenopos oocytes injected with in vitro transcribed chi-1 RNA did not demonstrate agonist-activated currents. Pairwise expression of chi-1 with members of the AMPA, KA, or delta class of glutamate receptor subunits either failed to generate agonist-activated currents or failed to alter the underlying current generated by the coexpressed subunit. However, coexpression of chi-1 with subunits forming otherwise functional NMDA receptors resulted in an inhibition of current responses. Since chi-1 did not alter the currents generated by non-NMDA subunits, this suggests that chi-1 may specifically interact with NMDA receptor subunits. Further characterization will be required to establish the precise role of this glutamate receptor subunit in neuronal signaling.
    BibTeX:
    @article{CIABARRA1995,
      author = {CIABARRA, AM and SULLIVAN, JM and GAHN, LG and PECHT, G and HEINEMANN, S and SEVARINO, KA},
      title = {CLONING AND CHARACTERIZATION OF CHI-1 - A DEVELOPMENTALLY-REGULATED MEMBER OF A NOVEL CLASS OF THE IONOTROPIC GLUTAMATE-RECEPTOR FAMILY},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1995},
      volume = {15},
      number = {10},
      pages = {6498-6508}
    }
    
    Clark, R., Zola, S. & Squire, L. Impaired recognition memory in rats after damage to the hippocampus {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({23}), pp. {8853-8860} 
    article  
    Abstract: Rats with radio-frequency or ibotenic acid lesions of the hippocampus and rats with radio-frequency lesions of the fornix were tested on the visual paired comparison task (VPC), a test of recognition memory. Memory was assessed at five different delay intervals ranging from 10 sec to 24 hr. All operated groups performed normally at the shorter delays (10 sec and 1 min). Across longer delays, the two groups with hippocampal damage were impaired. Rats with fornix lesions performed well on the VPC task but were impaired on a spatial task (spontaneous alternation). The results show that the hippocampus is essential for normal recognition memory. Moreover, fornix lesions need not mimic the effects of direct damage to hippocampal tissue. The findings are discussed in the context of the contribution of the hippocampus to recognition memory.
    BibTeX:
    @article{Clark2000,
      author = {Clark, RE and Zola, SM and Squire, LR},
      title = {Impaired recognition memory in rats after damage to the hippocampus},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {23},
      pages = {8853-8860}
    }
    
    COFFEY, C., WILKINSON, W., WEINER, R., PARASHOS, I., DJANG, W., WEBB, M., FIGIEL, G. & SPRITZER, C. QUANTITATIVE CEREBRAL ANATOMY IN DEPRESSION - A CONTROLLED MAGNETIC-RESONANCE-IMAGING STUDY {1993} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {50}({1}), pp. {7-16} 
    article  
    Abstract: Magnetic resonance imaging was used to examine cerebral anatomy in 48 inpatients with severe depression who were referred for electroconvulsive therapy and in 76 normal control subjects. The magnetic resonance imaging measures included determinations of regional cerebral volumes and ratings of the frequency and severity of cortical atrophy, lateral ventricular enlargement, and subcortical hyperintensity. The mean total frontal lobe volume was found to be 7% smaller in the inpatients with severe depression (235.88 mL) than in the normal control subjects (254.32 mL)-a difference that was statistically significant even after adjusting for the effects of age, sex, education, and intracranial size. No group differences were observed in the volumes of the cerebral hemispheres, the temporal lobes, or the amygdala-hippocampal complex, nor in the frequency of cortical atrophy. Neither did the groups differ with respect to the total volumes of the lateral and third ventricles, nor in the frequency of lateral ventricular enlargement. Patients with depression had a significantly higher frequency of subcortical hyperintensity in the periventricular white matter, with an odds ratio of 5.32.
    BibTeX:
    @article{COFFEY1993,
      author = {COFFEY, CE and WILKINSON, WE and WEINER, RD and PARASHOS, IA and DJANG, WT and WEBB, MC and FIGIEL, GS and SPRITZER, CE},
      title = {QUANTITATIVE CEREBRAL ANATOMY IN DEPRESSION - A CONTROLLED MAGNETIC-RESONANCE-IMAGING STUDY},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      publisher = {AMER MEDICAL ASSOC},
      year = {1993},
      volume = {50},
      number = {1},
      pages = {7-16},
      note = {145TH ANNUAL MEETING OF THE AMERICAN PSYCHIATRIC ASSOC, WASHINGTON, DC, MAY 07, 1992}
    }
    
    Conner, J., Lauterborn, J., Yan, Q., Gall, C. & Varon, S. Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: Evidence for anterograde axonal transport {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({7}), pp. {2295-2313} 
    article  
    Abstract: A sensitive immunohistochemical technique was used, along with highly specific affinity-purified antibodies to brain-derived neurotrophic factor (BDNF), to generate a detailed mapping of BDNF immunoreactivity (BDNF-ir) throughout the adult rat CNS. A parallel analysis of sites of BDNF synthesis was performed with in situ hybridization techniques using a cRNA probe to the exon encoding mature rat BDNF protein. These combined data revealed (1) groups of cell bodies containing diffuse BDNF-ir throughout the CNS that were strongly correlated with fields of cells containing BDNF mRNA; (2) varying degrees of BDNF-ir outside of cell bodies, in what appeared to be fibers and/or terminals; and (3) many regions containing extremely heavy BDNF-immunoreactive fiber/terminal labeling what lacked BDNF mRNA (e.g., medial habenula, central nucleus of the amygdala, bed nucleus of stria terminalis, lateral septum, and spinal cord). The latter observation suggested that in these regions BDNF was derived from anterograde axonal transport by afferent systems. In the two cases in which this hypothesis was tested by the elimination of select afferents, BDNF immunostaining was completely eliminated. These data, along with the observation that BDNF-ir was rarely found within dendrites or fibers en passage, suggest that BDNF protein produced in adult CNS neurons is polarized primarily along axonal processes and is preferentially stored in terminals within the innervation target.
    BibTeX:
    @article{Conner1997,
      author = {Conner, JM and Lauterborn, JC and Yan, Q and Gall, CM and Varon, S},
      title = {Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: Evidence for anterograde axonal transport},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {7},
      pages = {2295-2313}
    }
    
    Cornea-Hebert, V., Riad, M., Wu, C., Singh, S. & Descarries, L. Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat {1999} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {409}({2}), pp. {187-209} 
    article  
    Abstract: Light and electron microscope immunocytochemistry with a monoclonal antibody against the N-terminal domain of the human protein was used to determine the cellular and subcellular localization of serotonin 5-HT2A receptors in the central nervous system of adult rat. Following immunoperoxidase or silver-intensified immunogold labeling, neuronal, somatodendritic, and/or axonal immunoreactivity was detected in numerous brain regions, including all those in which ligand binding sites and 5-HT2A mRNA had previously been reported. The distribution of 5-HT2A-immunolabeled soma/dendrites was characterized in cerebral cortex, olfactory system, septum, hippocampal formation, basal ganglia, amygdala, diencephalon, cerebellum, brainstem, and spinal cord. Labeled axons were visible in every myelinated tract known to arise from immunoreactive cell body groups. In immunopositive soma/dendrites as well as axons, the 5-HT2A receptor appeared mainly cytoplasmic rather than membrane bound. Even though the dendritic labeling was generally stronger than the somatic, it did not extend to dendritic spines in such regions as the cerebral and piriform cortex, the neostriatum, or the molecular layer of the cerebellum. Similarly, there were no labeled axon terminals in numerous regions known to be strongly innervated by the immunoreactive somata and their axons (e.g., molecular layer of piriform cortex). It was concluded that the 5-HT2A receptor is mostly intracellular and transported in dendrites and axons, but does not reach into dendritic spines or axon terminals. Because it has previously been shown that this serotonin receptor is transported retrogradely as well as anterogradely, activates intracellular transduction pathways and intervenes in the regulation of the expression of many genes, it is suggested that one of its main functions is to participate in retrograde signaling systems activated by serotonin. (C) 1999 Wiley-Liss, inc.
    BibTeX:
    @article{Cornea-Hebert1999,
      author = {Cornea-Hebert, V and Riad, M and Wu, C and Singh, SK and Descarries, L},
      title = {Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1999},
      volume = {409},
      number = {2},
      pages = {187-209}
    }
    
    COSTA, E. & GUIDOTTI, A. DIAZEPAM BINDING INHIBITOR (DBI) - A PEPTIDE WITH MULTIPLE BIOLOGICAL ACTIONS {1991} LIFE SCIENCES
    Vol. {49}({5}), pp. {325-344} 
    article  
    Abstract: Diazepam binding inhibitor (DBI) is a 9-kD polypeptide that was first isolated in 1983 from rat brain by monitoring its ability to displace diazepam from the benzodiazepine (BZD) recognition site located on the extracellular domain of the type A receptor for gamma-aminobutyric acid (GABA(A) receptor) and from the mitochondrial BZD receptor (MBR) located on the outer mitochondrial membrane. In brain, DBI and its two major processing products [DBI 33-50, or octadecaneuropeptide (ODN) and DBI 17-50, or triakontatetraneuropeptide (TTN)] are unevenly distributed in neurons, with the highest concentrations of DBI (10 to 50-mu-M) being present in the hypothalamus, amygdala, cerebellum, and discrete areas of the thalamus, hippocampus, and cortex. DBI is also present in specialized glial cells (astroglia and Bergmann glia) and in peripheral tissues. In the periphery, the highest concentration of DBI occurs in cells of the zona glomerulosa and fasciculata of the adrenal cortex and in Leydig cells of the testis; interestingly, these are the same cell types in which MBRs are highly concentrated. Stimulation of MBRs by appropriate ligands (including DBI and TTN) facilitates cholesterol influx into mitochondria and the subsequent formation of pregnenolone, the parent molecule for endogenous steroid production; this facilitation occurs not only in peripheral steroidogenic tissues, but also in glial cells, the steroidogenic cells of the brain. Some of the steroids (pregnenolone sulfate, dehydroepiandrosterone sulfate, 3-alpha-hydroxy-5-alpha-pregnan-20-one, and 3-alpha, 21-dihydroxy-5-alpha-pregnan-20-one) produced in brain (neurosteroids) function as potent (with effects in the nanomolar concentration range) positive or negative allosteric modulators of GABA(A) receptor function. Thus, accumulating evidence suggests that the various neurobiological actions of DBI and its processing products may be attributable to the ability of these peptides either to bind to BZD recognition sites associated with GABA(A) receptors or to bind to glial cell MBRs and modulate the rate and quality of neurosteroidogenesis. The neurobiological effects of DBI and its processing products in physiological and pathological conditions (hepatic encephalopathy, depression, panic) concentrations may therefore be explained by interactions with different types of BZD recognition site. In addition, recent reports that DBI and some of its fragments inhibit (in nanomolar concentrations) glucose-induced insulin release from pancreatic islets and bind acyl-coenzyme A with high affinity support the hypothesis that DBI is a precursor of biologically active peptides with multiple actions in the brain and in peripheral tissues.
    BibTeX:
    @article{COSTA1991,
      author = {COSTA, E and GUIDOTTI, A},
      title = {DIAZEPAM BINDING INHIBITOR (DBI) - A PEPTIDE WITH MULTIPLE BIOLOGICAL ACTIONS},
      journal = {LIFE SCIENCES},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1991},
      volume = {49},
      number = {5},
      pages = {325-344}
    }
    
    Critchley, H., Corfield, D., Chandler, M., Mathias, C. & Dolan, R. Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans {2000} JOURNAL OF PHYSIOLOGY-LONDON
    Vol. {523}({1}), pp. {259-270} 
    article  
    Abstract: 1. States of peripheral autonomic arousal accompany emotional behaviour, physical exercise and cognitive effort, and their central representation may influence decision making and the regulation of social and emotional behaviours. However, the cerebral functional neuroanatomy representing and mediating peripheral autonomic responses in humans is poorly understood. 2. Six healthy volunteer subjects underwent (H2O)-O-15 positron emission tomography (PET) scanning while performing isometric exercise and mental arithmetic stressor tasks, and during corresponding control tasks. Mean arterial blood pressure (MAP) and heart rate (HR) were monitored during scanning. 3. Data were analysed using statistical parametric mapping (SPM99). Conjunction analyses were used to determine significant changes in regional cerebral blood flow (rCBF) during states of cardiovascular arousal common to both exercise and mental stressor tasks. 4. Exercise and mental stressor tasks, relative to their control tasks, were associated with significantly (P < 0.001) increased MAP and HR. Significant common activations (increased rCBF) were observed in cerebellar vermis, brainstem and right anterior cingulate. In both exercise and mental stress tasks, increased rCBF in cerebellar vermis, right anterior cingulate and right insula covaried with MAP; rCBF in pens, cerebellum and right insula covaried with HR. Cardiovascular arousal in both categorical and covariance analyses was associated with decreased rCBF in prefrontal and medial temporal regions. 5. Neural responses in discrete brain regions accompany peripheral cardiovascular arousal. We provide evidence for the involvement of areas previously implicated in cognitive and emotional behaviours in the representation of peripheral autonomic states, consistent with a functional organization that produces integrated cardiovascular response patterns in the service of volitional and emotional behaviours.
    BibTeX:
    @article{Critchley2000a,
      author = {Critchley, HD and Corfield, DR and Chandler, MP and Mathias, CJ and Dolan, RJ},
      title = {Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans},
      journal = {JOURNAL OF PHYSIOLOGY-LONDON},
      publisher = {CAMBRIDGE UNIV PRESS},
      year = {2000},
      volume = {523},
      number = {1},
      pages = {259-270}
    }
    
    Critchley, H., Daly, E., Bullmore, E., Williams, S., Van Amelsvoort, T., Robertson, D., Rowe, A., Phillips, M., McAlonan, G., Howlin, P. & Murphy, D. The functional neuroanatomy of social behaviour - Changes in cerebral blood flow when people with autistic disorder process facial expressions {2000} BRAIN
    Vol. {123}({Part 11}), pp. {2203-2212} 
    article  
    Abstract: Although high-functioning individuals with autistic disorder (i.e. autism and Asperger syndrome) are of normal intelligence,they have life-long abnormalities in social communication and emotional behaviour. However, the biological basis of social difficulties in autism is poorly understood. Facial expressions help shape behaviour, and we investigated if high-functioning people with autistic disorder show neurobiological differences from controls when processing emotional facial expressions. We used functional MRI to investigate brain activity in nine adults with autistic disorder (mean age +/- standard deviation 37 +/- 7 years; IQ 102 +/- 15) and nine controls (27 +/- 7 years; IQ 116 +/- 10) when explicitly (consciously) and implicitly (unconsciously) processing emotional facial expressions, Subjects with autistic disorder differed significantly from controls in the activity of cerebellar, mesolimbic and temporal lobe cortical regions of the brain when processing facial expressions. Notably, they did not activate a cortical `face area' when explicitly appraising expressions, or the left amygdala region and left cerebellum when implicitly processing emotional facial expressions, High-functioning people with autistic disorder have biological differences from controls when consciously and unconsciously processing facial emotions, and these differences are most likely to be neurodevelopmental in origin. This may account for some of the abnormalities in social behaviour associated with autism.
    BibTeX:
    @article{Critchley2000,
      author = {Critchley, HD and Daly, EM and Bullmore, ET and Williams, SCR and Van Amelsvoort, T and Robertson, DM and Rowe, A and Phillips, M and McAlonan, G and Howlin, P and Murphy, DGM},
      title = {The functional neuroanatomy of social behaviour - Changes in cerebral blood flow when people with autistic disorder process facial expressions},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {2000},
      volume = {123},
      number = {Part 11},
      pages = {2203-2212}
    }
    
    Critchley, H., Mathias, C. & Dolan, R. Neural activity in the human brain relating to uncertainty and arousal during anticipation {2001} NEURON
    Vol. {29}({2}), pp. {537-545} 
    article  
    Abstract: We used functional magnetic resonance neuroimaging to measure brain activity during delay between reward-related decisions and their outcomes, and the modulation of this delay activity by uncertainty and arousal. Feedback, indicating financial gain or loss, was given following a fixed delay. Anticipatory arousal was indexed by galvanic skin conductance. Delay-period activity was associated with bilateral activation in orbital and medial prefrontal, temporal, and right parietal cortices. During delay, activity in anterior cingulate and orbitofrontal cortices was modulated by outcome uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal cortices activity was modulated by degree of anticipatory arousal. A distinct region of anterior cingulate was commonly activated by both uncertainty and arousal. Our findings highlight distinct contributions of cognitive uncertainty and autonomic arousal to anticipatory neural activity in prefrontal cortex.
    BibTeX:
    @article{Critchley2001,
      author = {Critchley, HD and Mathias, CJ and Dolan, RJ},
      title = {Neural activity in the human brain relating to uncertainty and arousal during anticipation},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2001},
      volume = {29},
      number = {2},
      pages = {537-545}
    }
    
    CULLINAN, W., HERMAN, J. & WATSON, S. VENTRAL SUBICULAR INTERACTION WITH THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS - EVIDENCE FOR A RELAY IN THE BED NUCLEUS OF THE STRIA TERMINALIS {1993} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {332}({1}), pp. {1-20} 
    article  
    Abstract: The axonal projections of the ventral subiculum to the bed nucleus of the stria terminalis (BST) were examined in the rat with the anterograde neuronal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Axons originating in the ventral subiculum coursed to the BST through either the fimbria-fornix, or a pathway involving the stria terminalis via the amygdala. Ventral subicular axons gave rise to dense terminal networks that were preferentially distributed in medial and ventral subregions of the BST. The distribution of subicular fibers and terminals was examined in relation to BST neurons that project to the hypothalamic paraventricular nucleus (PVN). In these cases, discrete iontophoretic injections of the retrograde tracer Fluoro-gold were made in the PVN, with PHA-L delivered to the ipsilateral ventral subiculum. An immunocytochemical double-labeling protocol was then employed for the simultaneous detection of PHA-L and Fluoro-gold, and provided light microscopic evidence for subicular input to PVN-projecting cells located within the BST. In a second series of experiments, the gamma-amino butyric acid (GABA)ergic nature of the BST was examined by in situ hybridization histochemistry for detection of transcripts encoding GAD67 mRNA. The studies revealed that a high proportion of BST neurons express GAD67 transcripts. Also, experiments combining Fluoro-gold tracing with GAD67 in situ hybridization suggested that a proportion of PVN-projecting neurons in the BST are GABAergic. Taken together, the results of these sets of studies suggest that the inhibitory influences of the hippocampus on the PVN might be relayed through specific portions of the BST. These findings may have important implications for our understanding of the neural regulation of the hypothalamic-pituitary-adrenal axis.
    BibTeX:
    @article{CULLINAN1993,
      author = {CULLINAN, WE and HERMAN, JP and WATSON, SJ},
      title = {VENTRAL SUBICULAR INTERACTION WITH THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS - EVIDENCE FOR A RELAY IN THE BED NUCLEUS OF THE STRIA TERMINALIS},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1993},
      volume = {332},
      number = {1},
      pages = {1-20}
    }
    
    Dallman, M., Pecoraro, N., Akana, S., la Fleur, S., Gomez, F., Houshyar, H., Bell, M., Bhatnagar, S., Laugero, K. & Manalo, S. Chronic stress and obesity: A new view of ``comfort food'' {2003} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {100}({20}), pp. {11696-11701} 
    article DOI  
    Abstract: The effects of adrenal corticosteroids on subsequent adrenocorticotropin secretion are complex. Acutely (within hours), glucocorticoids (GCs) directly inhibit further activity in the hypothalamo-pituitary-adrenal axis, but the chronic actions (across days) of these steroids on brain are directly excitatory. Chronically high concentrations of GCs act in three ways that are functionally congruent. (i) GCs increase the expression of corticotropin-releasing factor (CRF) mRNA in the central nucleus of the amygdala, a critical node in the emotional brain. CRF enables recruitment of a chronic stress-response network. (h) GCs increase the salience of pleasurable or compulsive activities (ingesting sucrose, fat, and drugs, or wheel-running). This motivates ingestion of ``comfort food.'' (iii) GCs act systemically to increase abdominal fat depots. This allows an increased signal of abdominal energy stores to inhibit catecholamines in the brainstem and CRF expression in hypothalamic neurons regulating adrenocorticotropin. Chronic stress, together with high GC concentrations, usually decreases body weight gain in rats; by contrast, in stressed or depressed humans chronic stress induces either increased comfort food intake and body weight gain or decreased intake and body weight loss. Comfort food ingestion that produces abdominal obesity, decreases CRF mRNA in the hypothalamus of rats. Depressed people who overeat have decreased cerebrospinal CRF, catecholamine concentrations, and hypothalamo-pituitary-adrenal activity. We propose that people eat comfort food in an attempt to reduce the activity in the chronic stress-response network with its attendant anxiety. These mechanisms, determined in rats, may explain some of the epidemic of obesity occurring in our society.
    BibTeX:
    @article{Dallman2003,
      author = {Dallman, MF and Pecoraro, N and Akana, SF and la Fleur, SE and Gomez, F and Houshyar, H and Bell, ME and Bhatnagar, S and Laugero, KD and Manalo, S},
      title = {Chronic stress and obesity: A new view of ``comfort food''},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {2003},
      volume = {100},
      number = {20},
      pages = {11696-11701},
      doi = {{10.1073/pnas.1934666100}}
    }
    
    Dalton, K., Nacewicz, B., Johnstone, T., Schaefer, H., Gernsbacher, M., Goldsmith, H., Alexander, A. & Davidson, R. Gaze fixation and the neural circuitry of face processing in autism {2005} NATURE NEUROSCIENCE
    Vol. {8}({4}), pp. {519-526} 
    article DOI  
    Abstract: Diminished gaze fixation is one of the core features of autism and has been proposed to be associated with abnormalities in the neural circuitry of affect. We tested this hypothesis in two separate studies using eye tracking while measuring functional brain activity during facial discrimination tasks in individuals with autism and in typically developing individuals. Activation in the fusiform gyrus and amygdala was strongly and positively correlated with the time spent fixating the eyes in the autistic group in both studies, suggesting that diminished gaze fixation may account for the fusiform hypoactivation to faces commonly reported in autism. In addition, variation in eye fixation within autistic individuals was strongly and positively associated with amygdala activation across both studies, suggesting a heightened emotional response associated with gaze fixation in autism.
    BibTeX:
    @article{Dalton2005,
      author = {Dalton, KM and Nacewicz, BM and Johnstone, T and Schaefer, HS and Gernsbacher, MA and Goldsmith, HH and Alexander, AL and Davidson, RJ},
      title = {Gaze fixation and the neural circuitry of face processing in autism},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2005},
      volume = {8},
      number = {4},
      pages = {519-526},
      doi = {{10.1038/nn1421}}
    }
    
    Damasio, A. The somatic marker hypothesis and the possible functions of the prefrontal cortex {1996} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
    Vol. {351}({1346}), pp. {1413-1420} 
    article  
    Abstract: In this article I discuss a hypothesis, known as the somatic marker hypothesis, which I believe is relevant to the understanding of processes of human reasoning and decision making. The ventromedial sector of the prefrontal cortices is critical to the operations postulated here, but the hypothesis does not necessarily apply to prefrontal cortex as a whole and should not be seen as an attempt to unify frontal lobe functions under a single mechanism. The key idea in the hypothesis is that `marker' signals influence the processes of response to stimuli, at multiple levels of operation, some of which occur overtly (consciously, `in mind') and some of which occur covertly (non-consciously, in a non-minded manner). The marker signals arise in bioregulatory processes, including those which express themselves in emotions and feelings, but are not necessarily confined to those alone. This is the reason why the markers are termed somatic: they relate to body-state structure and regulation even when they do not arise in the body proper but rather in the brain's representation of the body. Examples of the covert action of `marker' signals are the undeliberated inhibition of a response learned previously; the introduction of a bias in the selection of an aversive or appetitive mode of behaviour, or in the otherwise deliberate evaluation of varied option-outcome scenarios. Examples of overt action include the conscious `qualifying' of certain option-outcome scenarios as dangerous or advantageous. The hypothesis rejects attempts to limit human reasoning and decision making to mechanisms relying, in an exclusive and unrelated manner, on either conditioning alone or cognition alone.
    BibTeX:
    @article{Damasio1996,
      author = {Damasio, AR},
      title = {The somatic marker hypothesis and the possible functions of the prefrontal cortex},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES},
      publisher = {ROYAL SOC LONDON},
      year = {1996},
      volume = {351},
      number = {1346},
      pages = {1413-1420}
    }
    
    Damasio, A., Grabowski, T., Bechara, A., Damasio, H., Ponto, L., Parvizi, J. & Hichwa, R. Subcortical and cortical brain activity during the feeling of self-generated emotions {2000} NATURE NEUROSCIENCE
    Vol. {3}({10}), pp. {1049-1056} 
    article  
    Abstract: In a series of [O-15]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.
    BibTeX:
    @article{Damasio2000,
      author = {Damasio, AR and Grabowski, TJ and Bechara, A and Damasio, H and Ponto, LLB and Parvizi, J and Hichwa, RD},
      title = {Subcortical and cortical brain activity during the feeling of self-generated emotions},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {2000},
      volume = {3},
      number = {10},
      pages = {1049-1056}
    }
    
    DAMASIO, A., TRANEL, D. & DAMASIO, H. INDIVIDUALS WITH SOCIOPATHIC BEHAVIOR CAUSED BY FRONTAL DAMAGE FAIL TO RESPOND AUTONOMICALLY TO SOCIAL-STIMULI {1990} BEHAVIOURAL BRAIN RESEARCH
    Vol. {41}({2}), pp. {81-94} 
    article  
    Abstract: Following damage to ventromedial frontal cortices, adults with previously normal personalities develop defects in decision-making and planning that are especially revealed in an abnormal social conduct. The defect repeatedly leads to negative personal consequences. The physiopathology of this disorder is an enigma. We propose that the defect is due to an inability to activate somatic states linked to punishment and reward, that were previously experienced in association with specific social situations, and that must be reactivated in connection with anticipated outcomes of response options. During the processing that follows the perception of a social event, the experience of certain anticipated outcomes of response options would be marked by the reactivation of an appropriate somatic state. Failure to reactivate pertinent somatic markers would deprive the individual of an automatic device to signal ultimately deleterious consequences relative to responses that might nevertheless bring immediate reward (or, alternatively, signal ultimately advantageous outcomes relative to responses that might bring immediate pain). As an example, activation of somatic markers would (1) force attention to future negative consequences, permitting conscious suppression of the responses leading to them and deliberate selection of biologically advantageous responses, and (2) trigger non-conscious inhibition of response states by engagement of subcortical neurotransmitter systems linked to appetitive behaviors. An investigation of this theory in patients with frontal damage reveals that their autonomic responses to socially meaningful stimuli are indeed abnormal, suggesting that such stimuli fail to activate somatic states at the most basic level. On the contrary, elementary unconditioned stimuli (e.g. a loud noise) produce normal autonomic responses.
    BibTeX:
    @article{DAMASIO1990,
      author = {DAMASIO, AR and TRANEL, D and DAMASIO, H},
      title = {INDIVIDUALS WITH SOCIOPATHIC BEHAVIOR CAUSED BY FRONTAL DAMAGE FAIL TO RESPOND AUTONOMICALLY TO SOCIAL-STIMULI},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1990},
      volume = {41},
      number = {2},
      pages = {81-94}
    }
    
    Danysz, W. & Parsons, C. Glycine and N-methyl-D-aspartate receptors: Physiological significance and possible therapeutic applications {1998} PHARMACOLOGICAL REVIEWS
    Vol. {50}({4}), pp. {597-664} 
    article  
    BibTeX:
    @article{Danysz1998,
      author = {Danysz, W and Parsons, CG},
      title = {Glycine and N-methyl-D-aspartate receptors: Physiological significance and possible therapeutic applications},
      journal = {PHARMACOLOGICAL REVIEWS},
      publisher = {AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS},
      year = {1998},
      volume = {50},
      number = {4},
      pages = {597-664}
    }
    
    Date, Y., Ueta, Y., Yamashita, H., Yamaguchi, H., Matsukura, S., Kangawa, K., Sakurai, T., Yanagisawa, M. & Nakazato, M. Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems {1999} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {96}({2}), pp. {748-753} 
    article  
    Abstract: We determined the immunohistochemical distributions of orexin-A and orexin-B, hypothalamic peptides that function in the regulation of feeding behavior and energy homeostasis. Orexin-A and -B neurons were restricted to the lateral and posterior hypothalamus, whereas both orexin-A and -B nerve fibers projected widely into the olfactory bulb, cerebral cortex, thalamus, hypothalamus, and brainstem, Dense populations of orexin containing fibers were present in the paraventricular thalamic nucleus, central gray, raphe nuclei, and locus coeruleus, Moderate numbers of these fibers were found in the olfactory bulb, insular, infralimbic and prelimbic cortex, amygdala, ventral, and dorsolateral parts of the suprachiasmatic nucleus, paraventricular nucleus except the lateral magnocellular division, arcuate nucleus, supramammillary nucleus, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, Small numbers of orexin fibers were present in the perirhinal, motor and sensory cortex, hippocampus, and supraoptic nucleus, and a very small number in the lateral magnocellular division of the paraventricular nucleus. Intracerebroventricular injections of orexins induced c-fos expression in the paraventricular thalamic nucleus, locus coeruleus, arcuate nucleus, central gray, raphe nuclei, nucleus of the solitary tract, dorsal motor nucleus of the vagus, suprachiasmatic nucleus, supraoptic nucleus, and paraventricular nucleus except the lateral magnocellular division. The unique neuronal distribution of orexins and their functional activation of neural circuits suggest specific complex roles of the peptides in autonomic and neuroendocrine control.
    BibTeX:
    @article{Date1999,
      author = {Date, Y and Ueta, Y and Yamashita, H and Yamaguchi, H and Matsukura, S and Kangawa, K and Sakurai, T and Yanagisawa, M and Nakazato, M},
      title = {Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1999},
      volume = {96},
      number = {2},
      pages = {748-753}
    }
    
    Davidson, R. Anxiety and affective style: Role of prefrontal cortex and amygdala {2002} BIOLOGICAL PSYCHIATRY
    Vol. {51}({1}), pp. {68-80} 
    article  
    Abstract: This article reviews the modern literature on two key aspects of the central circuitry of emotion: the prefrontal cortex (PFC) and the amydala. There are several different functional divisions of the PFC, including the dorsolateral, ventromedial, and orbital sectors. Each of these regions plays some role in affective processing that shares the feature of representing affect in the absence of immediate rewards and punishments as well as in different aspects of emotional regulation. The amygdala appears to be crucial for the learning of new stimulus-threat contingencies and also appears to be important in the expression of cue-specific fear. Individual differences in both tonic activation and phasic reactivity in this circuit play an important role in governing different aspects of anxiety. Emphasis is placed on affective chronometry, or the time course of emotional responding, as a key attribute of individual differences in propensity, for anxiety that is regulated by this circuitry. (C) 2002 Society of Biological Psychiatry.
    BibTeX:
    @article{Davidson2002a,
      author = {Davidson, RJ},
      title = {Anxiety and affective style: Role of prefrontal cortex and amygdala},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2002},
      volume = {51},
      number = {1},
      pages = {68-80}
    }
    
    Davidson, R. & Irwin, W. The functional neuroanatomy of emotion and affective style {1999} TRENDS IN COGNITIVE SCIENCES
    Vol. {3}({1}), pp. {11-21} 
    article  
    Abstract: Recently, there has been a convergence in lesion and neuroimaging data in the identification of circuits underlying positive and negative emotion in the human brain. Emphasis is placed on the prefrontal cortex (PFC) and the amygdala as two key components of this circuitry. Emotion guides action and organizes behaviour towards salient goals. To accomplish this, It is essential that the organism have a means of representing affect in the absence of immediate elicitors. It is proposed that the PFC plays a crucial role in affective working memory. The ventromedial sector of the PFC is most directly involved in the representation of elementary positive and negative emotional states while the dorsolateral PFC may be involved in the representation of the goal states towards which these elementary positive and negative states are directed. The amygdala has been consistently identified as playing a crucial role in both the perception of emotional cues and the production of emotional responses, with some evidence suggesting that it is particularly involved with fear-related negative affect. Individual differences in amygdala activation are implicated in dispositional affective styles and increased reactivity to negative incentives. The ventral striatum, anterior cingulate and insular cortex also provide unique contributions to emotional processing.
    BibTeX:
    @article{Davidson1999,
      author = {Davidson, RJ and Irwin, W},
      title = {The functional neuroanatomy of emotion and affective style},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {1999},
      volume = {3},
      number = {1},
      pages = {11-21}
    }
    
    Davidson, R., Jackson, D. & Kalin, N. Emotion, plasticity, context, and regulation: Perspectives from affective neuroscience {2000} PSYCHOLOGICAL BULLETIN
    Vol. {126}({6, Sp. Iss. SI}), pp. {890-909} 
    article DOI  
    Abstract: The authors present an overview of the neural bases of emotion. They underscore the role of the prefrontal cortex (PFC) and amygdala in 2 brood approach- and withdrawal-related emotion systems. Components and measures of affective style are identified. Emphasis is given to affective chronometry and a role for the PFC in this process is proposed. Plasticity in the central circuitry of emotion is considered, and implications of data showing experience-induced changes in the hippocampus for understanding psychopathology and stress-related symptoms are discussed. Two key forms of affective plasticity are described-context and regulation. A role for the hippocampus in context-dependent normal and dysfunctional emotional responding is proposed. Finally, implications of these data for understanding the impact on neural circuitry of interventions to promote positive affect and on mechanisms that govern health and disease are considered.
    BibTeX:
    @article{Davidson2000,
      author = {Davidson, RJ and Jackson, DC and Kalin, NH},
      title = {Emotion, plasticity, context, and regulation: Perspectives from affective neuroscience},
      journal = {PSYCHOLOGICAL BULLETIN},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {2000},
      volume = {126},
      number = {6, Sp. Iss. SI},
      pages = {890-909},
      doi = {{10.1037//0033-2909.126.6.890}}
    }
    
    Davidson, R., Pizzagalli, D., Nitschke, J. & Putnam, K. Depression: Perspectives from affective neuroscience {2002} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {53}, pp. {545-574} 
    article  
    Abstract: Depression is a disorder of the representation and regulation of mood and emotion. The circuitry underlying the representation and regulation of normal emotion and mood is reviewed, including studies at the animal level, human lesion studies, and human brain imaging studies. This corpus of data is used to construct a model of the ways in which affect can become disordered in depression. Research on the prefrontal cortex, anterior cingulate, hippocampus, and amygdala is reviewed and abnormalities in the structure and function of these different regions in depression is considered. The review concludes with proposals for the specific types of processing abnormalities that result from dysfunctions in different parts of this circuitry and offers suggestions for the major themes upon which future research in this area should be focused.
    BibTeX:
    @article{Davidson2002,
      author = {Davidson, RJ and Pizzagalli, D and Nitschke, JB and Putnam, K},
      title = {Depression: Perspectives from affective neuroscience},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      publisher = {ANNUAL REVIEWS},
      year = {2002},
      volume = {53},
      pages = {545-574}
    }
    
    Davidson, R., Putnam, K. & Larson, C. Dysfunction in the neural circuitry of emotion regulation - A possible prelude to violence {2000} SCIENCE
    Vol. {289}({5479}), pp. {591-594} 
    article  
    Abstract: Emotion is normally regulated in the human brain by a complex circuit consisting of the orbital frontal cortex, amygdala, anterior cingulate cortex, and several other interconnected regions. There are both genetic and environmental contributions to the structure and function of this circuitry. We posit that impulsive aggression and violence arise as a consequence of faulty emotion regulation. Indeed, the prefrontal cortex receives a major serotonergic projection, which is dysfunctional in individuals who show impulsive violence. Individuals vulnerable to faulty regulation of negative emotion are at risk for violence and aggression. Research on the neural circuitry of emotion regulation suggests new avenues of intervention for such at-risk populations.
    BibTeX:
    @article{Davidson2000a,
      author = {Davidson, RJ and Putnam, KM and Larson, CL},
      title = {Dysfunction in the neural circuitry of emotion regulation - A possible prelude to violence},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {2000},
      volume = {289},
      number = {5479},
      pages = {591-594}
    }
    
    Davies, P., Pistis, M., Hanna, M., Peters, J., Lambert, J., Hales, T. & Kirkness, E. The 5-HT3B subunit is a major determinant of serotonin-receptor function {1999} NATURE
    Vol. {397}({6717}), pp. {359-363} 
    article  
    Abstract: The neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) mediates rapid excitatory responses through ligand-gated channels (5-HT3 receptors). Recombinant expression of the only identified receptor subunit (5-HT3A) yields functional 5-HT3 receptors(1). However, the conductance of these homomeric receptors (sub-picosiemens) is too small to be resolved directly, and contrasts with a robust channel conductance displayed by neuronal 5-HT3 receptors (9-17pS)(2-7). Neuronal 5-HT3 receptors also display a permeability to calcium ions and a current-voltage relationship that differ from those of homomeric receptors(3-5,8) Here we describe a new class of 5-HT3-receptor subunit (5-HT3B). Transcripts of this subunit are co-expressed with the 5-HT3A subunit in the amygdala, caudate and hippocampus. Heteromeric assemblies of 5-HT3A and 5-HT3B subunits display a large single-channel conductance (16 pS), low permeability to calcium ions, and a current-voltage relationship which resembles that of characterized neuronal 5-HT3 channels. The heteromeric receptors also display distinctive pharmacological properties. Surprisingly, the M2 region of the 5-HT3B subunit lacks any of the structural features that are known to promote the conductance of related receptors. In addition to providing a new target for therapeutic agents, the 5-HT3B subunit will be a valuable resource for defining the molecular mechanisms of ion-channel function.
    BibTeX:
    @article{Davies1999,
      author = {Davies, PA and Pistis, M and Hanna, MC and Peters, JA and Lambert, JJ and Hales, TG and Kirkness, EF},
      title = {The 5-HT3B subunit is a major determinant of serotonin-receptor function},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1999},
      volume = {397},
      number = {6717},
      pages = {359-363}
    }
    
    Davis, M. Are different parts of the extended amygdala involved in fear versus anxiety? {1998} BIOLOGICAL PSYCHIATRY
    Vol. {44}({12}), pp. {1239-1247} 
    article  
    Abstract: Although there is a close correspondence between fear and anxiety and the study of fear in animals has been extremely valuable for understanding brain systems that are important for anxiety, it is equally clear that a richer animal model of human anxiety disorders would include measures of both stimulus-specific fear and something less stimulus specific, more akin to anxiety. Studies in patients with posttraumatic stress syndrome indicate these individuals seem to show normal fear reactions but abnormal anxiety measured with the acoustic startle reflex. Studies in rats, also using the startle reflex, indicate that highly processed explicit cue information (lights, tones, touch) activates the central nucleus of the amygdala, which ill turn activates hypothalamic and brain stem target areas involved in specific signs of fear. Somewhat less explicit information, such as that produced by exposure to a threating environment for several minutes or by intraventricular administration of the peptide corticotropin-releasing hormone may activate a brain area closely related to the amygdala, called the bed nucleus of the stria terminalis, which in turn activates hypothalamic and brain stem target areas involved in specific signs of fear or anxiety. Because the nature of this information may be less specific than that produced by an explicit cue, and of much longer duration, activation of the bed nucleus of the stria terminalis may be mope akin to anxiety than to fear. Biol Psychiatry 1998;44:1239-1247 (C) 1998 Society of Biological Psychiatry.
    BibTeX:
    @article{Davis1998,
      author = {Davis, M},
      title = {Are different parts of the extended amygdala involved in fear versus anxiety?},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1998},
      volume = {44},
      number = {12},
      pages = {1239-1247},
      note = {Research Symposium on Brain Neurocircuitry of Anxiety and Fear - Implications for Clinical Research and Practice, BOSTON, MA, MAR 26, 1998}
    }
    
    Davis, M. Neurobiology of fear responses: The role of the amygdala {1997} JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
    Vol. {9}({3}), pp. {382-402} 
    article  
    Abstract: Evidence from many different laboratories using a variety of experimental techniques and animal species indicates that the amygdala plays a crucial role in conditioned fear and anxiety, as well as attention. Many amygdaloid projection areas are critically involved in specific signs used to measure fear and anxiety. Electrical stimulation of the amygdala elicits a pattern of behaviors that mimic natural or conditioned fear. Lesions of the amygdala block innate or conditioned fear, as well as various measures of attention, and local infusions of drugs into the amygdala have anxiolytic effects in several behavioral tests. N-methyl-D-aspartate (NMDA) receptors in the amygdala may be important in the acquisition of conditioned fear, whereas non-NMDA receptors are important for the expression of conditioned fear. The peptide corticotropin-releasing hormone appears to be especially important in fear or anxiety and may act within the amygdala to orchestrate parts of the fear reaction.
    BibTeX:
    @article{Davis1997,
      author = {Davis, M},
      title = {Neurobiology of fear responses: The role of the amygdala},
      journal = {JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES},
      publisher = {AMER PSYCHIATRIC ASSOCIATION},
      year = {1997},
      volume = {9},
      number = {3},
      pages = {382-402}
    }
    
    DAVIS, M. THE ROLE OF THE AMYGDALA IN FEAR AND ANXIETY {1992} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {15}, pp. {353-375} 
    article  
    BibTeX:
    @article{DAVIS1992,
      author = {DAVIS, M},
      title = {THE ROLE OF THE AMYGDALA IN FEAR AND ANXIETY},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      publisher = {ANNUAL REVIEWS INC},
      year = {1992},
      volume = {15},
      pages = {353-375}
    }
    
    DAVIS, M., FALLS, W., CAMPEAU, S. & KIM, M. FEAR-POTENTIATED STARTLE - A NEURAL AND PHARMACOLOGICAL ANALYSIS {1993} BEHAVIOURAL BRAIN RESEARCH
    Vol. {58}({1-2}), pp. {175-198} 
    article  
    Abstract: The fear-potentiated startle paradigm has proven to be a useful system with which to analyze neural systems involved in fear and anxiety. This test measures conditioned fear by an increase in the amplitude of a simple reflex (the acoustic startle reflex) in the presence of a cue previously paired with a shock. Fear-potentiated startle is sensitive to a variety of drugs such as diazepam, morphine, and buspirone that reduce anxiety in people and can be measured reliably in humans when the eyeblink component of startle is elicited at a time when they are anticipating a shock. Electrical stimulation techniques suggest that a visual conditioned stimulus ultimately alters acoustic startle at a specific point along the acoustic startle pathway. The lateral, basolateral and central amygdaloid nuclei and the caudal branch of the ventral amygdalofugal pathway projecting to the brainstem are necessary for potentiated startle to occur. The central nucleus of the amygdala projects directly to one of the brainstem nuclei critical for startle and electrical stimulation of this nucleus increases startle amplitude. Chemical or electrolytic lesions of either the central nucleus or the lateral and basolateral nuclei of the amygdala block the expression of fear-potentiated startle. The perirhinal cortex, which projects directly to the lateral and basolateral amygdaloid nuclei, plays a critical role in the expression of fear-potentiated startle using either visual or auditory conditioned stimuli. These latter amygdaloid nuclei may actually be the site of plasticity for fear conditioning, because local infusion of the NMDA antagonist AP5 into these nuclei blocks the acquisition of fear-potentiated startle. On the other hand, the expression of fear-potentiated startle is blocked by local infusion of the non-NMDA ionotropic antagonist CNQX or the G-protein inactivating toxin, pertussis toxin, but not by AP5. Finally, we have begun to investigate brain systems that might be involved in the inhibition of fear. Local infusion of AP5 into the amygdala was found to block the acquisition of experimental extinction, a prototypical method for reducing fear. We have also established a reliable procedure for producing both external and conditioned inhibition of fear-potentiated startle and hope to eventually understand the neural systems involved in these phenomena.
    BibTeX:
    @article{DAVIS1993,
      author = {DAVIS, M and FALLS, WA and CAMPEAU, S and KIM, M},
      title = {FEAR-POTENTIATED STARTLE - A NEURAL AND PHARMACOLOGICAL ANALYSIS},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1993},
      volume = {58},
      number = {1-2},
      pages = {175-198},
      note = {International Symposium on Emotion and Memory, ITATIAIA, BRAZIL, AUG 23-25, 1992}
    }
    
    DAVIS, M., RAINNIE, D. & CASSELL, M. NEUROTRANSMISSION IN THE RAT AMYGDALA RELATED TO FEAR AND ANXIETY {1994} TRENDS IN NEUROSCIENCES
    Vol. {17}({5}), pp. {208-214} 
    article  
    Abstract: An impressive amount of evidence from many different laboratories using a variety of experimental techniques indicates that the amygdala plays a crucial role in the acquisition, consolidation and retention or expression of conditioned fear. Electrophysiological data are beginning to detail the transmitters and inter-amygdala connections that transmit information to, within, and out of the amygdala. In general, treatments that increase the excitability of amygdala output neurons in the basolateral nucleus (for example, by decreasing opiate and GABA transmission, and increasing noradrenergic transmission) improve aversive conditioning, whereas treatments that decrease excitability of these neurons (by increasing opiate and GABA transmission, and decreasing NMDA and noradrenergic transmission) retard aversive conditioning as well as producing anxiolytic effects in appropriate animal tests. A better understanding of brain systems that inhibit the amygdala, as well as the role of its very high levels of peptides, might eventually lead to the development of more effective pharmacological strategies for treating clinical anxiety and memory disorders.
    BibTeX:
    @article{DAVIS1994,
      author = {DAVIS, M and RAINNIE, D and CASSELL, M},
      title = {NEUROTRANSMISSION IN THE RAT AMYGDALA RELATED TO FEAR AND ANXIETY},
      journal = {TRENDS IN NEUROSCIENCES},
      publisher = {ELSEVIER SCI LTD},
      year = {1994},
      volume = {17},
      number = {5},
      pages = {208-214}
    }
    
    Davis, M. & Whalen, P. The amygdala: vigilance and emotion {2001} MOLECULAR PSYCHIATRY
    Vol. {6}({1}), pp. {13-34} 
    article  
    Abstract: Here we provide a review of the animal and human literature concerning the role of the amygdala in fear conditioning, considering its potential influence over autonomic and hormonal changes, motor behavior and attentional processes. A stimulus that predicts an aversive outcome will change neural transmission in the amygdala to produce the somatic, autonomic and endocrine signs of fear, as well as increased attention to that stimulus. It is now clear that the amygdala is also involved in learning about positively valenced stimuli as well as spatial and motor learning and this review strives to integrate this additional information. A review of available studies examining the human amygdala covers both lesion and electrical stimulation studies as well as the most recent functional neuroimaging studies. Where appropriate, we attempt to integrate basic information on normal amygdala function with our current understanding of psychiatric disorders, including pathological anxiety.
    BibTeX:
    @article{Davis2001,
      author = {Davis, M and Whalen, PJ},
      title = {The amygdala: vigilance and emotion},
      journal = {MOLECULAR PSYCHIATRY},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2001},
      volume = {6},
      number = {1},
      pages = {13-34}
    }
    
    Debiec, J., LeDoux, J. & Nader, K. Cellular and systems reconsolidation in the hippocampus {2002} NEURON
    Vol. {36}({3}), pp. {527-538} 
    article  
    Abstract: Cellular theories of memory consolidation posit that new memories require new protein synthesis in order to be stored. Systems consolidation theories posit that the hippocampus has a time-limited role in memory storage, after which the memory is independent of the hippocampus. Here, we show that intra-hippocampal infusions of the protein synthesis inhibitor anisomycin caused amnesia for a consolidated hippocampal-dependent contextual fear memory, but only if the memory was reactivated prior to infusion. The effect occurred even if reactivation was delayed for 45 days after training, a time when contextual memory is independent of the hippocampus. Indeed, reactivation of a hippocampus-independent memory caused the trace to again become hippocampus dependent, but only for 2 days rather than for weeks. Thus, hippocampal memories can undergo reconsolidation at both the cellular and systems levels.
    BibTeX:
    @article{Debiec2002,
      author = {Debiec, J and LeDoux, JE and Nader, K},
      title = {Cellular and systems reconsolidation in the hippocampus},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2002},
      volume = {36},
      number = {3},
      pages = {527-538}
    }
    
    Depue, R. & Collins, P. Neurobiology of the structure of personality: Dopamine, facilitation of incentive motivation, and extraversion {1999} BEHAVIORAL AND BRAIN SCIENCES
    Vol. {22}({3}), pp. {491+} 
    article  
    Abstract: Extraversion has two central characteristics: (1) interpersonal engagement, which consists of affiliation (enjoying and valuing close interpersonal bonds, being warm and affectionate) and agency (being socially dominant, enjoying leadership roles, being assertive, being exhibitionistic, and having a sense of potency in accomplishing goals) and (2) impulsivity, which emerges from the interaction of extraversion and a second, independent trait (constraint). Agency is a more general motivational disposition that includes dominance, ambition, mastery, efficacy, and achievement. Positive affect (a combination of positive feelings and motivation) is closely associated with extraversion. Extraversion is accordingly based on positive incentive motivation. Parallels between extraversion (particularly its agency component) and a mammalian behavioral approach system based on positive incentive motivation implicate a neuroanatomical network and modulatory neurotransmitters in the processing of incentive motivation. A corticolimbic-striatal-thalamic network (1) integrates the salient incentive context in the medial orbital cortex, amygdala, and hippocampus; (2) encodes the intensity of incentive stimuli in a motive circuit composed of the nucleus accumbens, ventral pallidum, and ventral tegmental area dopamine projection system; and (3) creates an incentive motivational state that can be transmitted to the motor system. Individual differences in the functioning of this network arise from functional variation in the Ventral tegmental area dopamine projections, which are directly involved in coding the intensity of incentive motivation. The animal evidence suggests that there are three neurodevelopmental sources of individual differences in dopamine: genetic, ``experience-expectant,'' and ``experience-dependent.'' Individual differences in dopamine promote variation in the heterosynaptic plasticity that enhances the connection between incentive con text and incentive motivation and behavior. Our psychobiological threshold model explains the effects of individual differences in dopamine transmission on behavior, and their relation to personality traits is discussed.
    BibTeX:
    @article{Depue1999,
      author = {Depue, RA and Collins, PF},
      title = {Neurobiology of the structure of personality: Dopamine, facilitation of incentive motivation, and extraversion},
      journal = {BEHAVIORAL AND BRAIN SCIENCES},
      publisher = {CAMBRIDGE UNIV PRESS},
      year = {1999},
      volume = {22},
      number = {3},
      pages = {491+}
    }
    
    Derbyshire, S., Jones, A., Gyulai, F., Clark, S., Townsend, D. & Firestone, L. Pain processing during three levels of noxious stimulation produces differential patterns of central activity {1997} PAIN
    Vol. {73}({3}), pp. {431-445} 
    article  
    Abstract: Previous functional imaging studies have demonstrated a number of discrete brain structures that increase activity with noxious stimulation. Of the commonly identified central structures, only the anterior cingulate cortex shows a consistent response during the experience of pain. The insula and thalamus demonstrate reasonable consistency while all other regions, including the lentiform nucleus, somatosensory cortex and prefrontal cortex, are active in no more than half the current studies. The reason for such discrepancy is likely to be due in part to methodological variability and in part to individual variability. One aspect of the methodology which is likely to contribute is the stimulus intensity. Studies vary considerably regarding the intensity of the noxious and non-noxious stimuli delivered. This is likely to produce varying activation of central structures coding for the intensity, affective and cognitive components of pain. Using twelve healthy volunteers and positron emission tomography (PET), the regional cerebral blood flow (rCBF) responses to four intensities of stimulation were recorded. The stimulation was delivered by a CO2 laser and was described subjectively as either warm (not painful), pain threshold (just painful), mildly painful or moderately painful. The following group subtractions were made to examine the changing cerebral responses as the stimulus intensity increased: (1) just painful - warm; (2) mild pain - warm; and (3) moderate pain - warm. In addition, rCBF changes were correlated with the subjective stimulus ratings. The results for comparison `1' indicated activity in the contralateral prefrontal (area 10/46/44), bilateral inferior parietal (area 40) and ipsilateral premotor cortices (area 6), possibly reflecting initial orientation and plans for movement. The latter comparisons and correlation analysis indicated a wide range of active regions including bilateral prefrontal, inferior parietal and premotor cortices and thalamic responses, contralateral hippocampus, insula and primary somatosensory cortex and ipsilateral perigenual cingulate cortex (area 24) and medial frontal cortex (area 32). Decreased rCBF was observed in the amygdala region. These responses were interpreted with respect to their contribution to the multidimensional aspects of pain including fear avoidance, affect, sensation and motivation or motor initiation. It is suggested that future studies examine the precise roles of each particular region during the central processing of pain. (C) 1997 International Association for the Study of Pain. Published by Elsevier Science B.V.
    BibTeX:
    @article{Derbyshire1997,
      author = {Derbyshire, SWG and Jones, AKP and Gyulai, F and Clark, S and Townsend, D and Firestone, LL},
      title = {Pain processing during three levels of noxious stimulation produces differential patterns of central activity},
      journal = {PAIN},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1997},
      volume = {73},
      number = {3},
      pages = {431-445}
    }
    
    DeSouza, E. Corticotropin-releasing factor receptors: Physiology, pharmacology, biochemistry and role in central nervous system and immune disorders {1995} PSYCHONEUROENDOCRINOLOGY
    Vol. {20}({8}), pp. {789-819} 
    article  
    Abstract: Corticotropin-releasing factor (CRF) plays a major role in coordinating the endocrine, autonomic, behavioral and immune responses to stress through actions in the brain and the periphery. CRF receptors identified in brain, pituitary and spleen have comparable kinetic and pharmacological characteristics, guanine nucleotide sensitivity and adenylate cyclase-stimulating activity. Differences were observed in the molecular mass of the CRF receptor complex between the brain (58,000 Da) and the pituitary and spleen (75,000 Da), which appeared to be due to differential glycosylation of the receptor proteins. The recently cloned CRF receptor in the pituitary and the brain (designated as CRF(1)) encodes a 415 amino acid protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive intestinal peptide/growth hormone-releasing hormone subfamily of G-protein-coupled receptors. A second member of the CRF receptor family encoding a 411 amino acid rat brain protein with approximate to 70% homology to CRF(1) has recently been identified (designated as CRF(2)); there exists an additional splice variant of the CRF(2) receptor with a different N-terminal domain encoding a protein of 431 amino acids. In autoradiographic studies, CRF receptors were localized in highest densities in the anterior and intermediate lobes of the pituitary gland, olfactory bulb, cerebral cortex, amygdala, cerebellum and the macrophage-enriched zones and red pulp regions of the spleen. CRF can modulate the number of CRF receptors in a reciprocal manner. For example, stress and adrenalectomy increase hypothalamic CRF secretion which, in turn, down-regulates CRF receptors in the anterior pituitary. CRF receptors in the brain and pituitary are also altered as a consequence of the development and aging processes. In addition to a physiological role for CRF in integrating the responses of the brain, endocrine and immune systems to physiological, psychological and immunological stimuli, recent clinical data implicate CRF in the etiology and pathophysiology of various endocrine, psychiatric, neurologic and inflammatory illnesses. Hypersecretion of CRF in the brain may contribute to the symptomatology seen in neuropsychiatric disorders, such as depression, anxiety-related disorders and anorexia nervosa. Furthermore, overproduction of CRF at peripheral inflammatory sites, such as synovial joints may contribute to autoimmune diseases such as rheumatoid arthritis. In contrast, deficits in brain CRF are apparent in neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, as they relate to dysfunction of CRF neurons in the brain areas affected in the particular disorder. Strategies directed at developing CRF-related agents may hold promise for novel therapies for the treatment of these various disorders.
    BibTeX:
    @article{DeSouza1995,
      author = {DeSouza, EB},
      title = {Corticotropin-releasing factor receptors: Physiology, pharmacology, biochemistry and role in central nervous system and immune disorders},
      journal = {PSYCHONEUROENDOCRINOLOGY},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1995},
      volume = {20},
      number = {8},
      pages = {789-819}
    }
    
    DEVINSKY, O., MORRELL, M. & VOGT, B. CONTRIBUTIONS OF ANTERIOR CINGULATE CORTEX TO BEHAVIOUR {1995} BRAIN
    Vol. {118}({Part 1}), pp. {279-306} 
    article  
    Abstract: Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into `affect' and `cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition divi sion includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness alter affective stare and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to ties, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Over-all, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours. The anterior cingulate cortex is part of a larger matrix of structures that are engaged in similar functions. These structures from the rostral limbic system and include the amygdala, periaqueductal grey, ventral striatum, orbitofrontal and anterior insular cortices. The system formed by these interconnected areas assesses the motivational content of internal and external stimuli and regulates context-dependent behaviours.
    BibTeX:
    @article{DEVINSKY1995,
      author = {DEVINSKY, O and MORRELL, MJ and VOGT, BA},
      title = {CONTRIBUTIONS OF ANTERIOR CINGULATE CORTEX TO BEHAVIOUR},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS UNITED KINGDOM},
      year = {1995},
      volume = {118},
      number = {Part 1},
      pages = {279-306}
    }
    
    Di Chiara, G. Role of dopamine in the behavioural actions of nicotine related to addiction {2000} EUROPEAN JOURNAL OF PHARMACOLOGY
    Vol. {393}({1-3, Sp. Iss. SI}), pp. {295-314} 
    article  
    Abstract: Experimental impairment of dopamine function by 6-hydroxydopamine lesions or by dopamine receptor antagonists shows that dopamine is involved in nicotine's discriminative stimulus properties, nicotine-induced facilitation of intracranial self-stimulation, intravenous nicotine self-administration, nicotine conditioned place-preference and nicotine-induced disruption of latent inhibition. Therefore, nicotine depends on dopamine for those behavioural effects that are most relevant for its reinforcing properties and are likely to be the basis of the abuse liability of tobacco smoke. On the other hand, in vivo monitoring studies show that nicotine stimulates dopamine transmission in specific brain areas and in particular, in the shell of the nucleus accumbens and in areas of the extended amygdala. These effects of nicotine resemble those of a reward like food except that nicotine-induced release of dopamine does not undergo single-trial, long-lasting habituation. It is speculated that repeated non-habituating stimulation of dopamine release by nicotine in the nucleus accumbens shell abnormally facilitates associative stimulus-reward learning. Acute effects of nicotine on dopamine transmission undergo acute and chronic tolerance; with repeated, discontinuous exposure, sensitization of nicotine-induced stimulation of dopamine release in the nucleus accumbens core takes place while the response in the shell is reduced. It is speculated that these adaptive changes are the substrate of a switch from abnormal incentive responding controlled by consequences (action-outcome responding) into abnormal habit responding, triggered by conditional stimuli and automatically driven by action schemata relatively independent from nicotine reward. These two modalities might coexist, being utilized alternatively in relation to the availability of tobacco. Unavailability of tobacco disrupts the automatic, implicit modality of abnormal habit responding switching responding into the explicit, conscious modality of incentive drug-seeking and craving. (C) 2000 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{DiChiara2000,
      author = {Di Chiara, G},
      title = {Role of dopamine in the behavioural actions of nicotine related to addiction},
      journal = {EUROPEAN JOURNAL OF PHARMACOLOGY},
      publisher = {ELSEVIER SCIENCE BV},
      year = {2000},
      volume = {393},
      number = {1-3, Sp. Iss. SI},
      pages = {295-314},
      note = {Congress on Neuronal Nicotinic Receptors - From Stucture to Therapeutics, VENICE, ITALY, OCT 01-04, 1999}
    }
    
    Dickson, D. The pathogenesis of senile plaques {1997} JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
    Vol. {56}({4}), pp. {321-339} 
    article  
    Abstract: Senile plaques (SP) are complicated lesions composed of diverse amyloid peptides and associated molecules, degenerating neuronal processes, and reactive glia. Evidence suggests that diffuse, neurocentric amyloid deposits evolve over time with formation of discrete niduses that eventually become neuritic SP The evidence for differential amyloid precursor protein metabolism that may favor deposition of A beta 17-42 in this early, possibly aging-related lesion is discussed. This latter molecule, also known as P3, may represent a benign form of amyloid, since it lacks domains associated with activation and recruitment of glia to SP Subsequent to deposition of A beta 1-42 and then growth of the amyloid with precipitation of soluble A beta 1-40, in an Alzheimer disease-specific process, SP increasingly become associated with activated microglia and reactive astrocytes. In response to interaction with amyloid peptides and possibly glycated proteins, microglia and astrocytes produce a number of molecules that may be locally toxic to neuronal processes in the vicinity of SP, including cytokines, reactive oxygen and nitrogen intermediates, and proteases. They also produce factors that lead to their reciprocal activation and growth, which potentiate a local inflammatory cascade. Paired helical filament-(PHF) type neurites appear to be associated with SP only in so far as neurofibrillary degeneration has progressed to affect neurons in those regions where the plaque forms. Thus, PHF-type neurites are readily apparent in SP in the amygdala at an early stage, while they are late in primary cortices and never detected in cerebellar plaques, where only dystrophic neurites are detected. If the various stages of SP pathogenesis can be further clarified, it may be possible to develop rational approaches to therapy directed at site-, cell type-, and stage-specific interventions. Although controlling the local inflammatory microenvironment of SP may hold promise for slowing lesion pathogenesis, it still remains a fundamental challenge to determine the mechanism of neurodegeneration that results in widespread neurofibrillary degeneration and eventual synaptic and neuronal loss, which is considered to be the proximate cause of the clinical dementia syndrome.
    BibTeX:
    @article{Dickson1997,
      author = {Dickson, DW},
      title = {The pathogenesis of senile plaques},
      journal = {JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY},
      publisher = {AMER ASSN NEUROPATHOLOGISTS INC},
      year = {1997},
      volume = {56},
      number = {4},
      pages = {321-339}
    }
    
    Dimberg, U., Thunberg, M. & Elmehed, K. Unconscious facial reactions to emotional facial expressions {2000} PSYCHOLOGICAL SCIENCE
    Vol. {11}({1}), pp. {86-89} 
    article  
    Abstract: Studies reveal that when people are exposed to emotional facial expressions, they spontaneously react,with distinct facial electromyographic (EMG) reactions in emotion-relevant facial muscles. These reactions reflect, in part, a tendency to mimic the facial stimuli. We investigated whether corresponding facial reactions can be elicited when people are unconsciously exposed to happy and angry facial expressions. Through use of the backward-masking technique, the subjects were prevented from consciously perceiving 30-ms exposures of happy, neutral, and angry target faces, which immediately, were followed and masked by neutral faces. Despite the fact that exposure to happy and angry faces was unconscious, the subjects reacted with distinct facial muscle reactions that corresponded lo the happy and angry stimulus faces. Our results show that both positive and negative emotional reactions can be unconsciously evoked, and particularly that important. aspects of emotional face-to-face communication can occur on an unconscious level.
    BibTeX:
    @article{Dimberg2000,
      author = {Dimberg, U and Thunberg, M and Elmehed, K},
      title = {Unconscious facial reactions to emotional facial expressions},
      journal = {PSYCHOLOGICAL SCIENCE},
      publisher = {BLACKWELL PUBLISHERS},
      year = {2000},
      volume = {11},
      number = {1},
      pages = {86-89}
    }
    
    Ding, Y., Kaneko, T., Nomura, S. & Mizuno, N. Immunohistochemical localization of mu-opioid receptors in the central nervous system of the rat {1996} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {367}({3}), pp. {375-402} 
    article  
    Abstract: Of the three major types of opioid receptors (mu, delta, kappa) in the nervous system, mu-opioid receptor shows the highest affinity for morphine that exerts powerful effects on nociceptive, autonomic, and psychological functions. So far, at least two isoforms of mu-opioid receptors have been cloned from rat brain. The present study attempted to examine immunohistochemically the distribution of mu-opioid receptors in the rat central nervous system with two kinds of antibodies to recently cloned mu-opioid receptors (MOR1 and MOR1B). One antibody recognized a specific site for MOR1, and the other bound to a common site for MOR1 and MOR1B. Intense MOR1-like immunoreactivity (LI) was seen in the `patch' areas and subcallosal streak in the striatum, medial habenular nucleus, medial terminal nucleus of the accessory optic tract, interpeduncular nucleus, median raphe nucleus, parabrachial nuclei, locus coeruleus, ambiguus nucleus, nucleus of the solitary tract, and laminae I and II of the medullary and spinal dorsal horns. Many other regions, including the cerebral cortex, amygdala, thalamus, and hypothalamus, also contained many neuronal elements with MOR1-LI. The distribution pattern of the immunoreactivity revealed with the antibody to the common site for MOR1 and MOR1B (MOR1/1B-LI) was almost the same as that of MOR1-LI. Both MOR1-LI and MOR1/1B-LI were primarily located in neuronal cell bodies and dendrites. However, the immunoreactivities were observed in the accessory optic tract, fasciculus retroflexus, solitary tract, and primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns. The presynaptic location of MOR1-LI and MOR1/1B-LI was confirmed by lesion experiments: Enucleation, placing a lesion in the medial habenular nucleus, removal of the nodose ganglion, or dorsal rhizotomy resulted in a clear reduction of the immunoreactivities, respectively, in the nuclei of the accessory optic tract, some subnuclei of the interpeduncular nucleus, nucleus of the solitary tract, or laminae I and II of the spinal dorsal horn. The results indicate that the mu-opioid receptors are widely distributed in the brain and spinal cord, mainly postsynaptically and occasionally presynaptically. Opioids, including morphine, may inhibit the excitation of neurons via the postsynaptic mu-opioid receptors, and also suppress the release of neurotransmitters and/or neuromodulators from axon terminals through the presynaptic mu-opioid receptors. (C) 1996 Wiley-Liss, Inc.
    BibTeX:
    @article{Ding1996,
      author = {Ding, YQ and Kaneko, T and Nomura, S and Mizuno, N},
      title = {Immunohistochemical localization of mu-opioid receptors in the central nervous system of the rat},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1996},
      volume = {367},
      number = {3},
      pages = {375-402}
    }
    
    DIORIO, D., VIAU, V. & MEANEY, M. THE ROLE OF THE MEDIAL PREFRONTAL CORTEX (CINGULATE GYRUS) IN THE REGULATION OF HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSES TO STRESS {1993} JOURNAL OF NEUROSCIENCE
    Vol. {13}({9}), pp. {3839-3847} 
    article  
    Abstract: In the studies reported here we have examined the role of the medial prefrontal cortex (MpFC) in regulating hypothalamic-pituitary-adrenal (HPA) activity under basal and stressful conditions. In preliminary studies we characterized corticosteroid receptor binding in the rat MpFC. The results revealed high-affinity (K(d) approximately 1 nm) binding with a moderate capacity (42.9 +/- 3 fmol/mg) for H-3-aldosterone (with a 50-fold excess of cold RU28362; mineralocorticoid receptor) and high-affinity (K(d) approximately 0.5-1.0 nm) binding with higher capacity (1 83.2 +/- 22 fmol/mg) for H-3-RU 28362 (glucocorticoid receptor). Lesions of the MpFC (cingulate gyrus) significantly increased plasma levels of both adrenocorticotropin (ACTH) and corticosterone (CORT) in response to a 20 min restraint stress. The same lesions had no effect on hormone levels following a 2.5 min exposure to ether. Implants of crystalline CORT into the same region of the MpFC produced a significant decrease in plasma levels of both ACTH and CORT with restraint stress, but again, there was no effect with ether stress. Neither MpFC lesions nor CORT implants had any consistent effect on A.M. or P.M. levels of plasma ACTH or CORT. Manipulations of MpFC function were not associated with changes in the clearance rate for CORT or in corticosteroid receptor densities in the pituitary, hypothalamus, hippocampus, or amygdala. Taken together, these findings suggest that MpFC is a target site for the negative-feedback effects of glucocorticoids on stress-induced HPA activity, and that this effect is dependent upon the nature of the stress.
    BibTeX:
    @article{DIORIO1993,
      author = {DIORIO, D and VIAU, V and MEANEY, MJ},
      title = {THE ROLE OF THE MEDIAL PREFRONTAL CORTEX (CINGULATE GYRUS) IN THE REGULATION OF HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSES TO STRESS},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1993},
      volume = {13},
      number = {9},
      pages = {3839-3847}
    }
    
    Dolan, R. Emotion, cognition, and behavior {2002} SCIENCE
    Vol. {298}({5596}), pp. {1191-1194} 
    article  
    Abstract: Emotion is central to the quality and range of everyday human experience. The neurobiological substrates of human emotion are now attracting increasing interest within the neurosciences motivated, to a considerable extent, by advances in functional neuroimaging techniques. An emerging theme is the question of how emotion interacts with and influences other domains of cognition, in particular attention, memory, and reasoning. The psychological consequences and mechanisms underlying the emotional modulation of cognition provide the focus of this article.
    BibTeX:
    @article{Dolan2002,
      author = {Dolan, RJ},
      title = {Emotion, cognition, and behavior},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {2002},
      volume = {298},
      number = {5596},
      pages = {1191-1194}
    }
    
    Drevets, W. Prefrontal cortical-amygdalar metabolism in major depression {1999}
    Vol. {877}ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA - IMPLICATIONS FOR NEUROPSYCHIATRY AND DRUG ABUSE: IN HONOR OF LENNART HEIMER , pp. {614-637} 
    inproceedings  
    Abstract: Functional neuroimaging studies of the anatomical correlates of familial major depressive disorder (MDD) and bipolar disorder (BD) have identified abnormalities of resting blood flow (BF) and glucose metabolism in depression in the amygdala and the orbital and medial prefrontal cortical (PFC) areas that are extensively connected with the amygdala, The amygdala metabolism in MDD and ED is positively correlated with both depression severity and ``stressed'' plasma cortisol concentrations measured during scanning, During antidepressant drug treatment, the mean amygdala metabolism decreases in treatment responders, and the persistence of elevated amygdala metabolism during remission is associated with a high risk for the development of depressive relapse. The orbital C metabolism is also abnormally elevated during depression, but is negatively correlated with both depression severity and amygdala metabolism, suggesting that this structure may be activated as a compensatory mechanism to modulate amygdala activity or amygdala-driven emotional responses. The posterior orbital C and anterior cingulate C ventral to the genu of the corpus callosum (subgenual PFC) have more recently been shown in morphometric MRI and/or post mortem histopathological studies to have reduced grey matter volume and reduced glial cell numbers (with no equivalent loss of neurons) in familial MDD and ED. These data suggest a neural model in which dysfunction of limbic PFC structures impairs the modulation of the amygdala, leading to abnormal processing of emotional stimuli, Antidepressant drugs may compensate for this dysfunction by inhibiting pathological limbic activity.
    BibTeX:
    @inproceedings{Drevets1999a,
      author = {Drevets, WC},
      title = {Prefrontal cortical-amygdalar metabolism in major depression},
      booktitle = {ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA - IMPLICATIONS FOR NEUROPSYCHIATRY AND DRUG ABUSE: IN HONOR OF LENNART HEIMER },
      publisher = {NEW YORK ACAD SCIENCES},
      year = {1999},
      volume = {877},
      pages = {614-637},
      note = {Conference on Advancing from the Ventral Striatum to the Extended Amygdala - Implications for Neuropsychiatry and Drug Abuse-In Honor of Lennart Heimer, CHARLOTTESVILLE, VIRGINIA, OCT 18-21, 1998}
    }
    
    Drevets, W. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders {2001} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {11}({2}), pp. {240-249} 
    article  
    Abstract: Neuroimaging technology has provided unprecedented opportunities for elucidating the anatomical correlates of major depression. The knowledge gained from imaging research and from the postmortem studies that have been guided by imaging data is catalyzing a paradigm shift in which primary mood disorders are conceptualized as illnesses that involve abnormalities of brain structure, as well as of brain function. These data suggest specific hypotheses regarding the neural mechanisms underlying pathological emotional processing in mood disorders. They particularly support a role for dysfunction within the prefrontal cortical and striatal systems that normally modulate limbic and brainstem structures involved in mediating emotional behavior in the pathogenesis of depressive symptoms.
    BibTeX:
    @article{Drevets2001,
      author = {Drevets, WC},
      title = {Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      publisher = {CURRENT BIOLOGY LTD},
      year = {2001},
      volume = {11},
      number = {2},
      pages = {240-249}
    }
    
    Drevets, W. Neuroimaging studies of mood disorders {2000} BIOLOGICAL PSYCHIATRY
    Vol. {48}({8}), pp. {813-829} 
    article  
    Abstract: Neuroimaging studies of major depression have identified neurophysiologic abnormalities in multiple areas of the orbital and medial prefrontal cortex, the amygdala, and related parts of the striatum and thalamus. Some of these abnormalities appear mood state-dependent and are located in regions where cerebral blood flow increases during normal and other pathologic emotional states. These neurophysiologic differences between depressives and control subjects may thus implicate areas where physiologic activity changes to mediate or respond to the emotional, behavioral, and cognitive manifestations of major depressive episodes. Other abnormalities persist following symptom remission, and are found in orbital and medial prefrontal cortex areas where postmortem studies demonstrate reductions in colter volume and histopathologic changes in primary mood disorders. These areas appear to modulate emotional behavior and stress responses, based upon evidence from brain mapping, lesion analysis, and electrophysiologic studies of humans and/or experimental animals. Dysfunction involving these regions is thus hypothesized to play a role in the pathogenesis of depressive symptoms. Taken together, these findings implicate interconnected neural circuits in which pathologic patterns of neurotransmission may result in the emotional, motivational, cognitive, and behavioral manifestations of primary and secondary affective disorders. Biol Psychiatry 2000;48:813-829 (C) 2000 Society of Biological Psychiatry.
    BibTeX:
    @article{Drevets2000,
      author = {Drevets, WC},
      title = {Neuroimaging studies of mood disorders},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2000},
      volume = {48},
      number = {8},
      pages = {813-829},
      note = {Conference on Depression in the 21st Century: New Insight into Drug Development and Neurobiology, DANA POINT, CA, FEB 02-22, 2000}
    }
    
    Drevets, W., Frank, E., Price, J., Kupfer, D., Holt, D., Greer, P., Huang, Y., Gautier, C. & Mathis, C. PET imaging of serotonin 1A receptor binding in depression {1999} BIOLOGICAL PSYCHIATRY
    Vol. {46}({10}), pp. {1375-1387} 
    article  
    Abstract: Background: The serotonin-1A (5HT1A) receptor system has been implicated in the pathophysiology of major depression by postmortem studies of suicide victims and depressed subjects dying of natural causes. This literature is in disagreement, however, regarding the brain regions where 5HT1A receptor binding differs between depressives and controls and the direction of such differences relative to the normal baseline, possibly reflecting the diagnostic heterogeneity inherent within suicide samples. PET imaging using the 5HT1A receptor radioligand, [C-11]WAY-100635, may clarify the clinical conditions under which 5HT1A receptor binding potential (RP) is abnormal in depression. Methods: Regional 5HT1A receptor BP values were compared between 12 unmedicated depressives with primary, recurrent, familial mood disorders and 8 healthy controls using PET and [carbonyl-C-11]WAY-100635. Regions-of-interest (ROI) assessed were the mesiotemporal cortex (hippocampus-amygdala) and midbrain raphe, where previous postmortem studies suggested 5HT1A receptor binding is abnormal in depression. Results: The mean 5HT1A receptor BP was reduced 41.5% in the raphe (p <.02) and 26.8% in the mesiotemporal cortex (p <.025) in the depressives relative to the controls. Post hoc comparisons showed the abnormal reduction in 5HT1A receptor BP was not limited to these regions, but extended to control ROI in the occipital cortex and postcentral gyrus as well. The magnitude of these abnormalities was most prominent in bipolar depressives (n = 4) and unipolar depressives with bipolar relatives (n = 4). Conclusions: Serotonin-1A receptor BP is abnormally decreased in the depressed phase of familial mood disorders in multiple brain regions. Of the regions tested, the magnitude of this reduction was most prominent in the midbrain raphe. Converging evidence from postmortem studies of mood disorders suggests these reductions of 5HT1A receptor BP may be associated with histopathological changes involving the raphe. Biol Psychiatry 1999;46:1375-1387 (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Drevets1999,
      author = {Drevets, WC and Frank, E and Price, JC and Kupfer, DJ and Holt, D and Greer, PJ and Huang, YY and Gautier, C and Mathis, C},
      title = {PET imaging of serotonin 1A receptor binding in depression},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1999},
      volume = {46},
      number = {10},
      pages = {1375-1387}
    }
    
    Drevets, W. & Raichle, M. Reciprocal suppression of regional cerebral blood flow during emotional versus higher cognitive processes: Implications for interactions between emotion and cognition {1998} COGNITION & EMOTION
    Vol. {12}({3}), pp. {353-385} 
    article  
    Abstract: Brain mapping studies using dynamic imaging methods demonstrate areas where regional cerebral blood flow (rCBF) decreases, as well as areas where flow increases, during performance of various experimental tasks. Task specificity holds for both sets of cerebral blood flow changes (Delta CBF), respectively, providing the opportunity to investigate areas that become ``deactivated'' and ``activated'' in the experimental condition relative to the control state. Such data yield the intriguing observation that in areas implicated in emotional processing, such as the amygdala, the posteromedial orbital cortex, and the ventral anterior cingulate cortex, although flow increases as expected during specific emotion-related tasks, flow decreases during performance of some attentionally demanding, cognitive tasks. Conversely, in some of the areas that appear to subserve cognitive functions, such as the dorsal anterior cingulate and the dorsolateral prefrontal cortices, flow increases while performing attentionally demanding cognitive tasks, but decreases during some experimentally induced and pathological emotional states. Although the specific nature of such reciprocal patterns of regional Delta CBF remains unclear, they may reflect an important cross-modal interaction during mental operations. The possibility that neural activity is less active in areas required in emotional processing during some higher cognitive processes holds implications for the mechanisms underlying interactions between cognition and emotion. Furthermore, the possibility that neural activity in some cognitive-processing areas is suppressed during intense emotional states suggests mechanisms by which extreme fear or severe depression may interfere with cognitive performance.
    BibTeX:
    @article{Drevets1998,
      author = {Drevets, WC and Raichle, ME},
      title = {Reciprocal suppression of regional cerebral blood flow during emotional versus higher cognitive processes: Implications for interactions between emotion and cognition},
      journal = {COGNITION & EMOTION},
      publisher = {PSYCHOLOGY PRESS},
      year = {1998},
      volume = {12},
      number = {3},
      pages = {353-385}
    }
    
    DREVETS, W., VIDEEN, T., PRICE, J., PRESKORN, S., CARMICHAEL, S. & RAICHLE, M. A FUNCTIONAL ANATOMICAL STUDY OF UNIPOLAR DEPRESSION {1992} JOURNAL OF NEUROSCIENCE
    Vol. {12}({9}), pp. {3628-3641} 
    article  
    Abstract: The functional neuroanatomy of unipolar major depression was investigated using positron emission tomography to measure differences in regional cerebral blood flow (BF). A relatively homogeneous subject group was obtained using criteria for familial pure depressive disease (FPDD), which are based upon family history as well as upon symptoms and course. Because of the absence of certain knowledge about the pathophysiology of mood disorders and their underlying functional neuroanatomy, we used data obtained from the subtraction of composite images from one-half of depressed and control subjects to identify candidate regions of interest. The major cortical region defined in this manner was statistically tested on a second set of subjects. Using this strategy, we found increased BF in an area that extended from the left ventrolateral prefrontal cortex onto the medial prefrontal cortical surface. Based upon the connectivity between these portions of the prefrontal cortex and the amygdala and evidence that the amygdala is involved in emotional modulation, activity was measured in the left amygdala and found to be significantly increased in the depressed group. A separate group of subjects with FPDD who were currently asymptomatic were also imaged to determine whether these findings represented abnormalities associated with the depressed state, or with a trait difference that might underlie the tendency to become depressed. Only the depressed group had increased activity in the left prefrontal cortex, suggesting that this abnormality represents a state marker of FPDD. Both the depressed and the remitted groups demonstrated increased activity in the left amygdala, though this difference achieved significance only in the depressed group. This suggests that the abnormality involving the left amygdala may represent a trait marker of FPDD, though further assessment in a larger sample size is necessary to establish this. These data along with other evidence suggest that a circuit involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus is involved in the functional neuroanatomy of depression.
    BibTeX:
    @article{DREVETS1992,
      author = {DREVETS, WC and VIDEEN, TO and PRICE, JL and PRESKORN, SH and CARMICHAEL, ST and RAICHLE, ME},
      title = {A FUNCTIONAL ANATOMICAL STUDY OF UNIPOLAR DEPRESSION},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1992},
      volume = {12},
      number = {9},
      pages = {3628-3641}
    }
    
    DURING, M., RYDER, K. & SPENCER, D. HIPPOCAMPAL GABA TRANSPORTER FUNCTION IN TEMPORAL-LOBE EPILEPSY {1995} NATURE
    Vol. {376}({6536}), pp. {174-177} 
    article  
    Abstract: ELECTROPHYSIOLOGICAL studies of human temporal-lobe epilepsy suggest that a loss of hippocampal GABA-mediated inhibition may underlie the neuronal hyperexcitability(1-3). However, GABA (gamma-aminobutyric acid)-containing cells are preserved(4) and GABA receptors are maintained in the surviving hippocampal neurons(5). Diminished GABA release may therefore mediate the loss of inhibition. Here we show that, in the human brain, potassium-stimulated release of GABA was increased, and glutamate-induced, calcium-independent release of GABA was markedly decreased, in epileptogenic hippocampi, in contrast with contralateral, non-epileptogenic hippocampi. The glutamate-induced GABA release in vivo was transporter-mediated in rats. Furthermore, in amygdala-kindled rats, a model for human epilepsy, a decease in glutamate-induced GABA release was associated with a 48% decrease in tbe number of GABA transporters. These data suggest that temporal-lobe epilepsy is characterized in part by a loss of glutamate-stimulated GABA release that is secondary to a reduction in the number of GABA transporters.
    BibTeX:
    @article{DURING1995,
      author = {DURING, MJ and RYDER, KM and SPENCER, DD},
      title = {HIPPOCAMPAL GABA TRANSPORTER FUNCTION IN TEMPORAL-LOBE EPILEPSY},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1995},
      volume = {376},
      number = {6536},
      pages = {174-177}
    }
    
    DURING, M. & SPENCER, D. EXTRACELLULAR HIPPOCAMPAL GLUTAMATE AND SPONTANEOUS SEIZURE IN THE CONSCIOUS HUMAN BRAIN {1993} LANCET
    Vol. {341}({8861}), pp. {1607-1610} 
    article  
    Abstract: An alteration in excitatory and inhibitory influences may underlie epilepsy. We used bilateral intrahippocampal microdialysis to test the hypothesis that an increase in extracellular glutamate may trigger spontaneous seizures. The concentrations of glutamate and gamma-aminobutyric acid (GABA), the brain's major inhibitory neutrotransmitter, were measured in microdialysates before and during seizures in 6 patients with complex partial epilepsy investigated before surgery. Before seizures, concentrations of glutamate were higher in the epileptogenic hippocampus, whereas GABA concentrations were lower. During seizures, there was a sustained increase in extracellular glutamate to potentially neurotoxic concentrations in the epileptogenic hippocampus. Moreover, the increase preceded seizure. GABA concentrations were unchanged before seizures, but increased during them, with a greater rise in the non-epileptogenic hippocampus, suggesting that a rise in extracellular glutamate may precipitate seizures and that the concentrations reached may cause cell death.
    BibTeX:
    @article{DURING1993,
      author = {DURING, MJ and SPENCER, DD},
      title = {EXTRACELLULAR HIPPOCAMPAL GLUTAMATE AND SPONTANEOUS SEIZURE IN THE CONSCIOUS HUMAN BRAIN},
      journal = {LANCET},
      publisher = {LANCET LTD},
      year = {1993},
      volume = {341},
      number = {8861},
      pages = {1607-1610}
    }
    
    Emery, N. The eyes have it: the neuroethology, function and evolution of social gaze {2000} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {24}({6}), pp. {581-604} 
    article  
    Abstract: Gaze is an important component of social interaction. The function, evolution and neurobiology of gaze processing are therefore of interest to a number of researchers. This review discusses the evolutionary role of social gaze in vertebrates (focusing on primates), and a hypothesis that this role has changed substantially for primates compared to other animals. This change may have been driven by morphological changes to the face and eyes of primates, limitations in the facial anatomy of other vertebrates, changes in the ecology of the environment in which primates live, and a necessity to communicate information about the environment, emotional and mental states. The eyes represent different levels of signal value depending on the status, disposition and emotional state of the sender and receiver of such signals. There are regions in the monkey and human brain which contain neurons that respond selectively to faces, bodies and eye gaze. The ability to follow another individual's gaze direction is affected in individuals with autism and other psychopathological disorders, and after particular localized brain lesions. The hypothesis that gaze following is ``hard-wired'' in the brain, and may be localized within a circuit linking the superior temporal sulcus, amygdala and orbitofrontal cortex is discussed. (C) 2000 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Emery2000,
      author = {Emery, NJ},
      title = {The eyes have it: the neuroethology, function and evolution of social gaze},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2000},
      volume = {24},
      number = {6},
      pages = {581-604}
    }
    
    ERICSSON, A., KOVACS, K. & SAWCHENKO, P. A FUNCTIONAL ANATOMICAL ANALYSIS OF CENTRAL PATHWAYS SUBSERVING THE EFFECTS OF INTERLEUKIN-1 ON STRESS-RELATED NEUROENDOCRINE NEURONS {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({2}), pp. {897-913} 
    article  
    Abstract: Systemic administration of the cytokine interleukin-1 (IL-1) results in increased secretion of ACTH and corticosterone in rats. The available evidence suggests that the acute effects of IL-1 are exerted ultimately at the level of the hypothalamus to increase corticotropin-releasing factor (CRF) secretion into the hypophyseal portal circulation, and hence the central drive on the pituitary-adrenal system. However, the route(s) and mechanism(s) by which circulating IL-1 gains access to central mechanisms governing pituitary-adrenal output remain poorly understood. In this study, we show that intravenous injection of IL-1 beta provokes time- and dose-dependent increases in the expression of the immediate-early gene c-fos, in identified CRF and oxytocin-producing cells of the paraventricular nucleus of the hypothalamus (PVH). Several cell groups known to be involved in central visceromotor regulation also displayed comparable time- and dose-related activation to systemic IL-1, including the bed nucleus of the stria terminalis, the central nucleus of the amygdala, the lateral parabrachial nucleus, and cell groups of the dorsomedial and ventrolateral medulla. Activation of circumventricular organs, which have been hypothesized to serve as central monitors of circulating IL-1, required doses roughly an order of magnitude above those required to activate CRF neurons in the PVH. Combined immunohistochemical and retrograde tracing experiments revealed many IL-1-responsive cells in the nucleus of the solitary tract and the ventrolateral medulla to be catecholaminergic and to project to the region of the PVH. Discrete and unilateral interruption of ascending catecholaminergic projections from the medulla attenuated IL-1-stimulated increases in Fos immunoreactivity and CRF mRNA in the PVH on the ipsilateral side. Disruption of descending projections from circumventricular structures associated with the lamina terminalis did not affeet IL-1-mediated Fos induction in the PVH. We conclude that medullary catecholaminergic projections to the PVH play either a mediating or a permissive role in the IL-1-induced activation of the central limb of the hypothalamo-pituitary-adrenal axis.
    BibTeX:
    @article{ERICSSON1994,
      author = {ERICSSON, A and KOVACS, KJ and SAWCHENKO, PE},
      title = {A FUNCTIONAL ANATOMICAL ANALYSIS OF CENTRAL PATHWAYS SUBSERVING THE EFFECTS OF INTERLEUKIN-1 ON STRESS-RELATED NEUROENDOCRINE NEURONS},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {2},
      pages = {897-913}
    }
    
    ERICSSON, A., LIU, C., HART, R. & SAWCHENKO, P. TYPE-1 INTERLEUKIN-1 RECEPTOR IN THE RAT-BRAIN - DISTRIBUTION, REGULATION, AND RELATIONSHIP TO SITES OF IL-1-INDUCED CELLULAR ACTIVATION {1995} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {361}({4}), pp. {681-698} 
    article  
    Abstract: Systemic interleukin-l (IL-1) activates the hypothalamo-pituitary-adrenal (HPA) axis, an effect exerted through increased synthesis and secretion of corticotropin-releasing factor (CRF) by parvicellular neurosecretory neurons. The site(s) and mechanism(s) through which circulating IL-1 may access central systems governing HPA axis output remain obscure. To identify potential cellular targets for blood-borne IL-1, we analyzed the distribution of mRNA encoding the rat type 1 IL-1 receptor (IL-1R1) in rat brain. Regional ribonuclease protection assays detected a single protected fragment corresponding to the membrane-bound form of the IL-1R1 mRNA in all areas analyzed. In situ hybridization revealed labeling predominantly over barrier-related cells, including the leptomeninges, non-tanycytic portions of the ependyma, the choroid plexus, and vascular endothelium. Low to moderate levels of the IL-1R1 mRNA were detected in just a few neuronal cell groups, including the basolateral nucleus of the amygdala, the arcuate nucleus of the hypothalamus, the trigeminal and hypoglossal motor nuclei, and the area postrema. No specific labeling for IL-1R1 mRNA was detected over neurons that respond to intravenous IL-1 beta by induction of transcription factor Fos, including hypophysiotropic CRF cells and brainstem catecholamine neurons. Injection of IL-1 beta did, however, provoke induction of mRNA encoding the immediate-early gene, NGFI-B, but not c-fos, in two major loci of IL-1R1 expression, vascular endothelial cells, and the area postrema. Intravenous injection of IL-1 beta acutely down-regulated IL-1R1 mRNA in perivascular cells, but not in neuronal cell groups. These results suggest the parenchymal sites of IL-1R1 expression in rat to be distinct from those reported previously in mouse. The common expression in both species of an IL-1R in non-neuronal elements highlights the possibility that IL-l-mediated activation of CRF neurons may result from cytokine-receptor interaction at vascular, and/or other barrier-related, sites to trigger release of secondary signalling molecules in a position to interact with components of HPA control circuitry. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{ERICSSON1995,
      author = {ERICSSON, A and LIU, C and HART, RP and SAWCHENKO, PE},
      title = {TYPE-1 INTERLEUKIN-1 RECEPTOR IN THE RAT-BRAIN - DISTRIBUTION, REGULATION, AND RELATIONSHIP TO SITES OF IL-1-INDUCED CELLULAR ACTIVATION},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1995},
      volume = {361},
      number = {4},
      pages = {681-698}
    }
    
    EVERITT, B., CADOR, M. & ROBBINS, T. INTERACTIONS BETWEEN THE AMYGDALA AND VENTRAL STRIATUM IN STIMULUS REWARD ASSOCIATIONS - STUDIES USING A 2ND-ORDER SCHEDULE OF SEXUAL REINFORCEMENT {1989} NEUROSCIENCE
    Vol. {30}({1}), pp. {63-75} 
    article  
    BibTeX:
    @article{EVERITT1989,
      author = {EVERITT, BJ and CADOR, M and ROBBINS, TW},
      title = {INTERACTIONS BETWEEN THE AMYGDALA AND VENTRAL STRIATUM IN STIMULUS REWARD ASSOCIATIONS - STUDIES USING A 2ND-ORDER SCHEDULE OF SEXUAL REINFORCEMENT},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1989},
      volume = {30},
      number = {1},
      pages = {63-75}
    }
    
    Everitt, B., Dickinson, A. & Robbins, T. The neuropsychological basis of addictive behaviour {2001} BRAIN RESEARCH REVIEWS
    Vol. {36}({2-3, Sp. Iss. SI}), pp. {129-138} 
    article  
    Abstract: The argument advanced in this review is that drug addiction can be understood in terms of normal learning and memory systems of the brain which, through the actions of chronically self-administered drugs, are pathologically subverted, thereby leading to the establishment of compulsive drug-seeking habits, strengthened by the motivational impact of drug-associated stimuli and occurring at the expense of other sources of reinforcement. We review data from our studies that have utilized procedures which reveal the various influences of pavlovian stimuli on goal-directed behaviour, namely discriminated approach, pavlovian-to-instrumental transfer and conditioned reinforcement, in order to demonstrate their overlapping and also unique neural bases. These fundamental studies are also reviewed in the context of the neural and psychological mechanisms underlying drug-seeking behaviour that is under the control of drug-associated environmental stimuli. The ways in which such drug-seeking behaviour becomes compulsive and habitual, as well as the propensity for relapse to drug-seeking even after long periods of relapse, are discussed in terms of the aberrant learning set in train by the effects of self-administered drugs on plastic processes in limbic cortical-ventral striatal systems. (C) 2001 Elsevier Science BY All rights reserved.
    BibTeX:
    @article{Everitt2001,
      author = {Everitt, BJ and Dickinson, A and Robbins, TW},
      title = {The neuropsychological basis of addictive behaviour},
      journal = {BRAIN RESEARCH REVIEWS},
      publisher = {ELSEVIER SCIENCE BV},
      year = {2001},
      volume = {36},
      number = {2-3, Sp. Iss. SI},
      pages = {129-138},
      note = {Symposium of the Swiss-National-Science-Foundation, WARTH, SWITZERLAND, MAR 29-31, 2001}
    }
    
    EVERITT, B., MORRIS, K., OBRIEN, A. & ROBBINS, T. THE BASOLATERAL AMYGDALA VENTRAL STRIATAL SYSTEM AND CONDITIONED PLACE PREFERENCE - FURTHER EVIDENCE OF LIMBIC STRIATAL INTERACTIONS UNDERLYING REWARD-RELATED PROCESSES {1991} NEUROSCIENCE
    Vol. {42}({1}), pp. {1-18} 
    article  
    Abstract: The effects on the expression of a conditioned place preference of bilateral, excitotoxic amino acid-induced lesions of the basolateral region of the amygdala, or the ventral striatum, or asymmetric, unilateral lesions of both structures were studied. The place preference was conditioned by exposing hungry rats to sucrose in a distinctive environment. Following acquisition, bilateral quisqualate-induced lesions of the basolateral amygdala, as well as bilateral quinolinate-induced lesions of the ventral striatum, abolished the conditioned place preference. Bilateral ventromedial, but not dorsolateral, quinolinate-induced caudate-putamen lesions attenuated the place preference. Combining a unilateral lesion of the basolateral amygdala with a contralateral lesion of the ventral striatum also disrupted the conditioned place preference. These data provide further support for the hypothesis that the basolateral amygdala and ventral striatum are important parts of a neural system subserving stimulus-reward associations.
    BibTeX:
    @article{EVERITT1991,
      author = {EVERITT, BJ and MORRIS, KA and OBRIEN, A and ROBBINS, TW},
      title = {THE BASOLATERAL AMYGDALA VENTRAL STRIATAL SYSTEM AND CONDITIONED PLACE PREFERENCE - FURTHER EVIDENCE OF LIMBIC STRIATAL INTERACTIONS UNDERLYING REWARD-RELATED PROCESSES},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1991},
      volume = {42},
      number = {1},
      pages = {1-18}
    }
    
    Everitt, B., Parkinson, J., Olmstead, M., Arroyo, M., Robledo, P. & Robbins, T. Associative processes in addiction and reward - The role of amygdala-ventral striatal subsystems {1999}
    Vol. {877}ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA - IMPLICATIONS FOR NEUROPSYCHIATRY AND DRUG ABUSE: IN HONOR OF LENNART HEIMER , pp. {412-438} 
    inproceedings  
    Abstract: Only recently have the functional implications of the organization of the ventral striatum, amygdala, and related limbic-cortical structures, and their neuroanatomical interactions begun to be clarified. Processes of activation and reward have long been associated with the NAcc and its dopamine innervation, but the precise relationships between these constructs have remained elusive. We have sought to enrich our understanding of the special role of the ventral striatum in coordinating the contribution of different functional subsystems to confer flexibility, as well as coherence and vigor, to goal-directed behavior, through different forms of associative learning. Such appetitive behavior comprises many subcomponents, some of which we have isolated in these experiments to reveal that, not surprisingly, the mechanisms by which an animal sequences responding to reach a goal are complex. The data reveal how the different components, pavlovian approach (or sign-tracking), conditioned reinforcement (whereby pavlovian stimuli control goal-directed action), and also more general response-invigorating processes (often called ``activation,'' ``stress,'' or ``drive'') may be integrated within the ventral striatum through convergent interactions of the amygdala, other limbic cortical structures, and the mesolimbic dopamine system to produce coherent behavior. The position is probably not far different when considering aversively motivated behavior. Although it may be necessary to employ simplified, even abstract, paradigms for isolating these mechanisms, their concerted action can readily be appreciated in an adaptive, functional setting, such as the responding by rats for intravenous cocaine under a second-order schedule of reinforcement. Here, the interactions of primary reinforcement, psychomotor activation, pavlovian conditioning, and the control that drug cues exert over the integrated drug-seeking response can be seen to operate both serially and concurrently. The power of our analytic techniques for understanding complex motivated behavior has been evident for some time. However, the crucial point is that we are now able to map these components with increasing certainty onto discrete amygdaloid, and other Limbic cortical-ventral striatal subsystems. The neural dissection of these mechanisms also serves an important theoretical purpose in helping to validate the various hypothetical constructs and further developing theory. Major challenges remain, not the least of which is an understanding of the operation of the ventral striatum together with its dopaminergic innervation and its interactions with the basolateral amygdala, hippocampal formation, and prefrontal cortex at a more mechanistic, neuronal level.
    BibTeX:
    @inproceedings{Everitt1999,
      author = {Everitt, BJ and Parkinson, JA and Olmstead, MC and Arroyo, M and Robledo, P and Robbins, TW},
      title = {Associative processes in addiction and reward - The role of amygdala-ventral striatal subsystems},
      booktitle = {ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA - IMPLICATIONS FOR NEUROPSYCHIATRY AND DRUG ABUSE: IN HONOR OF LENNART HEIMER },
      publisher = {NEW YORK ACAD SCIENCES},
      year = {1999},
      volume = {877},
      pages = {412-438},
      note = {Conference on Advancing from the Ventral Striatum to the Extended Amygdala - Implications for Neuropsychiatry and Drug Abuse-In Honor of Lennart Heimer, CHARLOTTESVILLE, VIRGINIA, OCT 18-21, 1998}
    }
    
    Everitt, B. & Robbins, T. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion {2005} NATURE NEUROSCIENCE
    Vol. {8}({11}), pp. {1481-1489} 
    article DOI  
    Abstract: Drug addiction is increasingly viewed as the endpoint of a series of transitions from initial drug use-when a drug is voluntarily taken because it has reinforcing, often hedonic, effects-through loss of control over this behavior, such that it becomes habitual and ultimately compulsive. Here we discuss evidence that these transitions depend on interactions between pavlovian and instrumental learning processes. We hypothesize that the change from voluntary drug use to more habitual and compulsive drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation. These neural transitions may themselves depend on the neuroplasticity in both cortical and striatal structures that is induced by chronic self-administration of drugs.
    BibTeX:
    @article{Everitt2005,
      author = {Everitt, BJ and Robbins, TW},
      title = {Neural systems of reinforcement for drug addiction: from actions to habits to compulsion},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2005},
      volume = {8},
      number = {11},
      pages = {1481-1489},
      doi = {{10.1038/nn1579}}
    }
    
    Everitt, B. & Robbins, T. Central cholinergic systems and cognition {1997} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {48}, pp. {649-684} 
    article  
    Abstract: The organization and possible functions of basal forebrain and pontine cholinergic systems are reviewed. Whereas the basal forebrain cholinergic neuronal projections likely subserve a common electrophysiological function, e.g. to boost signal-to-noise ratios in cortical target areas, this function has different effects on psychological processes dependent upon the neural network operations within these various cortical domains. Evidence is presented that (a) the nucleus basalis-neocortical cholinergic system contributes greatly to visual attentional function, but not to mnemonic processes per se; (b) the septohippocampal projection is involved in the modulation of short-term spatial (working) memory processes, perhaps by prolonging the neural representation of external stimuli within the hippocampus; and (c) the diagonal band-cingulate cortex cholinergic projection impacts on the ability to utilize response rules through conditional discrimination. We also suggest that nucleus basalis-amygdala cholinergic projections have a role in the retention of affective conditioning while brainstem cholinergic projections to the thalamus and midbrain dopamine neurons affect basic arousal processes (e.g. sleep-wake cycle) and behavioral activation, respectively. The possibilities and limitations of therapeutic interventions with procholinergic drugs in patients with Alzheimer's disease and other neurodegenerative disorders in which basal forebrain cholinergic neurons degenerate are also discussed.
    BibTeX:
    @article{Everitt1997,
      author = {Everitt, BJ and Robbins, TW},
      title = {Central cholinergic systems and cognition},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      publisher = {ANNUAL REVIEWS INC},
      year = {1997},
      volume = {48},
      pages = {649-684}
    }
    
    FALLON, J., KOZIELL, D. & MOORE, R. CATECHOLAMINE INNERVATION OF BASAL FOREBRAIN .2. AMYGDALA, SUPRARHINAL CORTEX AND ENTORHINAL CORTEX {1978} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {180}({3}), pp. {509-531} 
    article  
    BibTeX:
    @article{FALLON1978,
      author = {FALLON, JH and KOZIELL, DA and MOORE, RY},
      title = {CATECHOLAMINE INNERVATION OF BASAL FOREBRAIN .2. AMYGDALA, SUPRARHINAL CORTEX AND ENTORHINAL CORTEX},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1978},
      volume = {180},
      number = {3},
      pages = {509-531}
    }
    
    FALLS, W., MISERENDINO, M. & DAVIS, M. EXTINCTION OF FEAR-POTENTIATED STARTLE - BLOCKADE BY INFUSION OF AN NMDA ANTAGONIST INTO THE AMYGDALA {1992} JOURNAL OF NEUROSCIENCE
    Vol. {12}({3}), pp. {854-863} 
    article  
    Abstract: Data derived from in vitro preparations indicate that NMDA receptors play a critical role in synaptic plasticity in the CNS. More recently, in vivo pharmacological manipulations have suggested that an NMDA-dependent process may be involved in specific forms of behavioral plasticity. All of the work thus far has focused on the possible role of NMDA receptors in the acquisition of responses. However, there are many examples in the behavioral literature of learning-induced changes that involve the reduction or elimination of a previously acquired response. Experimental extinction is a primary example of the elimination of a learned response. Experimental extinction is well described in the behavioral literature, but has not received the same attention in the neurobiological literature. As a result, the neural mechanisms that underlie this important form of learning are not at all understood. In the present experiments, the fear-potentiated startle paradigm was employed to begin to investigate neural mechanisms of extinction. The results show that infusion of the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (AP5) into the amygdala, a limbic structure known to be important for fear conditioning, dose-dependently blocked extinction of conditioned fear. Control experiments showed that the blockade of extinction was neither the result of the permanent disruption of amygdaloid function nor the result of decreased sensitivity of the animals to the conditioned stimulus. Infusion of AP5 into the interpositus nucleus of the cerebellum, a control site, did not block extinction. Finally, intra-amygdala infusion of a selected dose of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione did not block extinction of conditioned fear. These results, together with a previous report from our laboratory (Miserendino et al., 1990), demonstrate the importance of the amygdala in the elaboration of conditioned fear and suggest that an NMDA-dependent process might underlie the extinction of conditioned fear.
    BibTeX:
    @article{FALLS1992,
      author = {FALLS, WA and MISERENDINO, MJD and DAVIS, M},
      title = {EXTINCTION OF FEAR-POTENTIATED STARTLE - BLOCKADE BY INFUSION OF AN NMDA ANTAGONIST INTO THE AMYGDALA},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1992},
      volume = {12},
      number = {3},
      pages = {854-863}
    }
    
    Fanselow, M. Contextual fear, gestalt memories, and the hippocampus {2000} BEHAVIOURAL BRAIN RESEARCH
    Vol. {110}({1-2, Sp. Iss. SI}), pp. {73-81} 
    article  
    Abstract: This review examines the relationship between exploration and contextual fear conditioning. The fear acquired to places or contexts associated with aversive events is a form of Pavlovian conditioning. However, an initial period of exploration is necessary to allow the animal to form an integrated memory of the features of the context before conditioning can take place. The hippocampal formation plays a critical role in this process. Cells within the dorsal hippocampus are involved in the formation, storage and consolidation of this integrated representation of context. Projections from the subiculum to the nucleus accumbens regulate the exploration necessary for the acquisition of information about the features of the context. This model explains why electrolytic but not excitotoxic lesions of the dorsal hippocampus cause enhanced exploratory activity but both cause deficits in contextual fear. It also explains why retrograde amnesia of contextual fear is greater than anterograde amnesia. (C) 2000 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Fanselow2000,
      author = {Fanselow, MS},
      title = {Contextual fear, gestalt memories, and the hippocampus},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {2000},
      volume = {110},
      number = {1-2, Sp. Iss. SI},
      pages = {73-81},
      note = {Annual Meeting of the Pavlovian-Society, DUSSELDORF, GERMANY, OCT 30-NOV 01, 1998}
    }
    
    FANSELOW, M. NEURAL ORGANIZATION OF THE DEFENSIVE BEHAVIOR SYSTEM RESPONSIBLE FOR FEAR {1994} PSYCHONOMIC BULLETIN & REVIEW
    Vol. {1}({4}), pp. {429-438} 
    article  
    Abstract: This paper applies the behavior systems approach to fear and defensive behavior, examining the neural circuitry controlling fear and defensive behavior from this vantage point. The defensive behavior system is viewed as having three modes that are activated by different levels of fear. Low levels of fear promote pre-encounter defenses, such as meal-pattern reorganization. Moderate levels of fear activate post-encounter defenses. For the rat, freezing is the dominant post-encounter defensive response. Since this mode of defense is activated by learned fear, forebrain structures such as the amygdala play a critical role in its organization. Projections from the amygdala to the ventral periaqueductal gray activate freezing. Extremely high levels of fear, such as those provoked by physical contact, elicit the vigorous active defenses that compose the circa-strike mode. Midbrain structures such as the dorsolateral periaqueductal gray and the superior colliculus play a crucial role in organizing this mode of defense. Inhibitory interactions between the structures mediating circa-strike and post-encounter defense allow for the rapid switching between defensive modes as the threatening situation varies.
    BibTeX:
    @article{FANSELOW1994,
      author = {FANSELOW, MS},
      title = {NEURAL ORGANIZATION OF THE DEFENSIVE BEHAVIOR SYSTEM RESPONSIBLE FOR FEAR},
      journal = {PSYCHONOMIC BULLETIN & REVIEW},
      publisher = {PSYCHONOMIC SOC INC},
      year = {1994},
      volume = {1},
      number = {4},
      pages = {429-438}
    }
    
    FANSELOW, M. & KIM, J. ACQUISITION OF CONTEXTUAL PAVLOVIAN FEAR CONDITIONING IS BLOCKED BY APPLICATION OF AN NMDA RECEPTOR ANTAGONIST D,L-2-AMINO-5-PHOSPHONOVALERIC ACID TO THE BASOLATERAL AMYGDALA {1994} BEHAVIORAL NEUROSCIENCE
    Vol. {108}({1}), pp. {210-212} 
    article  
    Abstract: Rats, with chronic cannula placed bilaterally in the amygdala, received infusions of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV) before contextual Pavlovian fear conditioning. Administration of APV to the basolateral nucleus prevented acquisition of fear. Central nucleus infusions had no effect. It is concluded that an NMDA-mediated process near the basolateral region of the amygdala (e.g., lateral or basolateral nucleus) is essential for the learning of fear.
    BibTeX:
    @article{FANSELOW1994a,
      author = {FANSELOW, MS and KIM, JJ},
      title = {ACQUISITION OF CONTEXTUAL PAVLOVIAN FEAR CONDITIONING IS BLOCKED BY APPLICATION OF AN NMDA RECEPTOR ANTAGONIST D,L-2-AMINO-5-PHOSPHONOVALERIC ACID TO THE BASOLATERAL AMYGDALA},
      journal = {BEHAVIORAL NEUROSCIENCE},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1994},
      volume = {108},
      number = {1},
      pages = {210-212}
    }
    
    Fanselow, M. & LeDoux, J. Why we think plasticity underlying pavlovian fear conditioning occurs in the basolateral amygdala {1999} NEURON
    Vol. {23}({2}), pp. {229-232} 
    article  
    BibTeX:
    @article{Fanselow1999,
      author = {Fanselow, MS and LeDoux, JE},
      title = {Why we think plasticity underlying pavlovian fear conditioning occurs in the basolateral amygdala},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {1999},
      volume = {23},
      number = {2},
      pages = {229-232}
    }
    
    Fendt, M. & Fanselow, M. The neuroanatomical and neurochemical basis of conditioned fear {1999} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {23}({5}), pp. {743-760} 
    article  
    Abstract: After a few pairings of a threatening stimulus with a formerly neutral cue, animals and humans will experience a state of conditioned fear when only the cue is present. Conditioned fear provides a critical survival-related function in the face of threat by activating a range of protective behaviors. The present review summarizes and compares the results of different laboratories investigating the neuroanatomical and neurochemical basis of conditioned fear, focusing primarily on the behavioral models of freezing and fear-potentiated startle in rats. On the basis of these studies, we describe the pathways mediating and modulating fear. We identify several key unanswered questions and discuss possible implications for the understanding of human anxiety disorders. (C) 1999 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Fendt1999,
      author = {Fendt, M and Fanselow, MS},
      title = {The neuroanatomical and neurochemical basis of conditioned fear},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1999},
      volume = {23},
      number = {5},
      pages = {743-760}
    }
    
    Ferguson, J., Aldag, J., Insel, T. & Young, L. Oxytocin in the medial amygdala is essential for social recognition in the mouse {2001} JOURNAL OF NEUROSCIENCE
    Vol. {21}({20}), pp. {8278-8285} 
    article  
    Abstract: Oxytocin (OT) knock-out mice fail to recognize familiar conspecifics after repeated social exposures, despite normal olfactory and spatial learning abilities. OT treatment fully restores social recognition. Here we demonstrate that OT acts in the medial amygdala during the initial exposure to facilitate social recognition. OT given before, but not after, the initial encounter restores social recognition in OT knock-out mice. Using c-Fos immunoreactivity (Fos-IR) as a marker of neuronal activation in this initial encounter, we found similar neuronal activation in the wild-type (WT) and OT knock-out mouse in olfactory bulbs, piriform cortex, cortical amygdala, and the lateral septum. Wild-type, but not OT knock-out mice exhibited an induction of Fos-IR in the medial amygdala. Projections sites of the medial amygdala also failed to show a Fos-IR induction in the OT knock-out mice. OT knock-out, but not WT, mice showed dramatic increases in Fos-IR in the somatosensory cortex and the hippocampus, suggesting alternative processing of social cues in these animals. With site-specific injections of OT and an OT antagonist, we demonstrate that OT receptor activation in the medial amygdala is both necessary and sufficient for social recognition in the mouse.
    BibTeX:
    @article{Ferguson2001,
      author = {Ferguson, JN and Aldag, JM and Insel, TR and Young, LJ},
      title = {Oxytocin in the medial amygdala is essential for social recognition in the mouse},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2001},
      volume = {21},
      number = {20},
      pages = {8278-8285}
    }
    
    FILIPEK, P., RICHELME, C., KENNEDY, D. & CAVINESS, V. YOUNG-ADULT HUMAN BRAIN - AN MRI-BASED MORPHOMETRIC ANALYSIS {1994} CEREBRAL CORTEX
    Vol. {4}({4}), pp. {344-360} 
    article  
    Abstract: Morphometric analysis was performed on three-dimensional MRI scans of 10 male and 10 female young adults with four principal objectives: (1) to characterize in vivo volumes of whole brain and substructures, (2) to explore volumetric symmetry in bilateral structures, (3) to consider the extent to which volumetric measures are dimorphic in the male and female brain, and (4) to provide a normal volumetric database for the young adult brain. Total brain volumes ranged between 1173 and 1626 cm(3). All bilateral structures were symmetric or nearly symmetric in volume, with the exception of a slightly larger right neocortex and amygdala, and larger left lateral ventricle. Male brains were larger in volume than female brains, a difference that reached significance for cerebellar but not for cerebral hemisphere volume. In females, there was less cerebral white matter while caudate volume was larger than in the male brains. The proportions of caudate and hippocampus relative to total cerebral volumes were larger in females than in males. These four measures accurately predicted gender in 85% of the subjects by discriminant analysis. No gender differences were noted in the structural symmetry analysis. These results represent the first step in establishing a comprehensive database of morphometric parameters, with unexpected findings relative to brain symmetry and sexual dimorphism.
    BibTeX:
    @article{FILIPEK1994,
      author = {FILIPEK, PA and RICHELME, C and KENNEDY, DN and CAVINESS, VS},
      title = {YOUNG-ADULT HUMAN BRAIN - AN MRI-BASED MORPHOMETRIC ANALYSIS},
      journal = {CEREBRAL CORTEX},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1994},
      volume = {4},
      number = {4},
      pages = {344-360}
    }
    
    Filipek, P., SemrudClikeman, M., Steingard, R., Renshaw, P., Kennedy, D. & Biederman, J. Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls {1997} NEUROLOGY
    Vol. {48}({3}), pp. {589-601} 
    article  
    Abstract: Objective: To test by MRI-based morphometry the a priori hypotheses that developmental anomalies exist in attention-deficit hyperactivity disorder (ADHD) in left caudate and right prefrontal/frontal/ and/or posterior parietal hemispheric regions, in accord with neurochemical, neuronal circuitry and attentional network hypotheses, and prior imaging studies. Design: Case-control study. Setting: Academic medical center, Participants: Fifteen male subjects with ADHD without comorbid diagnoses (aged 12.4 +/- 3.4 years) and 15 male normal controls (aged 14.4 +/- 3.4), group-matched for age, IQ, and handedness. Main outcome measures: Global and hemispheric regional volumes (in cm(3)) of cerebral hemispheres, cortex, white matter, ventricles, caudate, lenticulate, central gray nuclei, insula, amygdala, and hippocampus. Results: Despite similar hemispheric volumes, ADHD subjects had smaller volumes of (1) left total caudate and caudate head (p < 0.04), with reversed asymmetry (p < 0.03); (2) right anterior-superior (frontal) region en bloc(p < 0.03) and white matter (p < 0.01); (3) bilateral anterior-inferior region en bloc(p < 0.04); and (4) bilateral retrocallosal (parietal-occipital) region white matter (p < 0.03). Possible structural correlates of ADHD response to stimulants were noted in an exploratory analysis, with the smallest and symmetric caudate, and smallest left anterior-superior cortex volumes found in the responders, but reversed caudate asymmetry and the smallest retrocallosal white matter volumes noted in the nonresponders, Conclusions, This study is the first to report localized hemispheric structural anomalies in ADHD, which are concordant with theoretical models of abnormal frontal-striatal and parietal function, and with possible differing morphologic substrates of response to stimulant medication.
    BibTeX:
    @article{Filipek1997,
      author = {Filipek, PA and SemrudClikeman, M and Steingard, RJ and Renshaw, PF and Kennedy, DN and Biederman, J},
      title = {Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls},
      journal = {NEUROLOGY},
      publisher = {LIPPINCOTT-RAVEN PUBL},
      year = {1997},
      volume = {48},
      number = {3},
      pages = {589-601}
    }
    
    Fink, G., Markowitsch, H., Reinkemeier, M., Bruckbauer, T., Kessler, J. & Heiss, W. Cerebral representation of one's own past: Neural networks involved in autobiographical memory {1996} JOURNAL OF NEUROSCIENCE
    Vol. {16}({13}), pp. {4275-4282} 
    article  
    Abstract: We studied the functional anatomy of affect-laden autobiographical memory in normal volunteers. Using (H2O)-O-15 positron emission tomography (PET), we measured changes in relative regional cerebral blood flow (rCBF). Four rCBF measurements were obtained during three conditions: REST, i.e., subjects lay at rest (for control); IMPERSONAL, i.e., subjects listened to sentences containing episodic information taken from an autobiography of a person they did not know, but which had been presented to them before PET scanning (nonautobiographical episodic memory ecphory); and PERSONAL, i.e., subjects listened to sentences containing information taken from their own past (autobiographical episodic memory ecphory). Comparing IMPERSONAL with REST (nonautobiographical episodic memory ecphory) resulted in relative rCBF increases symmetrically in both temporal robes including the temporal poles and medial and superior temporal gyri. The same loci, however, with a stronger lateralization to the right hemisphere were activated in the comparison PERSONAL to REST (autobiographical episodic memory ecphory). In addition, the right temporomesial, right dorsal prefrontal, right posterior cingulate areas, and the left cerebellum were activated. A comparison of PERSONAL and IMPERSONAL (autobiographical vs nonautobiographical episodic memory ecphory) demonstrated a preponderantly right hemispheric activation including primarily right temporomesial and temporolateral cortex, right posterior cingulate areas, right insula, and right prefrontal areas. The right temporomesial activation included hippocampus, parahippocampus, and amygdala. These results suggest that a right hemispheric network of temporal, together with posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect-laden autobiographical information.
    BibTeX:
    @article{Fink1996,
      author = {Fink, GR and Markowitsch, HJ and Reinkemeier, M and Bruckbauer, T and Kessler, J and Heiss, WD},
      title = {Cerebral representation of one's own past: Neural networks involved in autobiographical memory},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1996},
      volume = {16},
      number = {13},
      pages = {4275-4282}
    }
    
    Fischl, B., Salat, D., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., van der Kouwe, A., Killiany, R., Kennedy, D., Klaveness, S., Montillo, A., Makris, N., Rosen, B. & Dale, A. Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain {2002} NEURON
    Vol. {33}({3}), pp. {341-355} 
    article  
    Abstract: We present a technique for automatically assigning a neuroanatomical label to each voxel in an MRI volume based on probabilistic information automatically estimated from a manually labeled training set. In contrast to existing segmentation procedures that only label a small number of tissue classes, the current method assigns one of 37 labels to each voxel, including left and right caudate, putamen, pallidum, thalamus, lateral ventricles, hippocampus, and amygdala. The classification technique employs a registration procedure that is robust to anatomical variability, including the ventricular enlargement typically associated with neurological diseases and aging. The technique is shown to be comparable in accuracy to manual labeling, and of sufficient sensitivity to robustly detect changes in the volume of noncortical structures that presage the onset of probable Alzheimer's disease.
    BibTeX:
    @article{Fischl2002,
      author = {Fischl, B and Salat, DH and Busa, E and Albert, M and Dieterich, M and Haselgrove, C and van der Kouwe, A and Killiany, R and Kennedy, D and Klaveness, S and Montillo, A and Makris, N and Rosen, B and Dale, AM},
      title = {Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2002},
      volume = {33},
      number = {3},
      pages = {341-355}
    }
    
    Fox, N., Warrington, E., Freeborough, P., Hartikainen, P., Kennedy, A., Stevens, J. & Rossor, M. Presymptomatic hippocampal atrophy in Alzheimer's disease - A longitudinal MRI study {1996} BRAIN
    Vol. {119}({Part 6}), pp. {2001-2007} 
    article  
    Abstract: The hippocampal formation (HF) is known from pathological and MRI studies to be severely atrophied in established Alzheimer's disease. However it is unclear when the earliest changes in the HF occur: We performed a longitudinal study of asymptomatic individuals at risk of autosomal dominant familial Alzheimer's disease in order to assess presymptomatic changes in the HF. Seven at risk members of a familial Alzheimer's disease pedigree associated with the amyloid precursor protein 717 valine to glycine mutation underwent serial MR scanning and neuropsychological assessments over 3 years. These assessments were compared with results from 38 normal controls. During the study three at risk subjects became clinically affected Volumetric measurement of the HF showed that asymmetrical atrophy developed in these subjects before the appearance of symptoms. Verbal and visual memory measures declined in parallel with hippocampal loss. A loss of up to 8% per annum of the volume of the HF occurred in the 2 years over which symptoms first appeared. These findings may have implications for early diagnosis of Alzheimer's disease.
    BibTeX:
    @article{Fox1996,
      author = {Fox, NC and Warrington, EK and Freeborough, PA and Hartikainen, P and Kennedy, AM and Stevens, JM and Rossor, MN},
      title = {Presymptomatic hippocampal atrophy in Alzheimer's disease - A longitudinal MRI study},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {1996},
      volume = {119},
      number = {Part 6},
      pages = {2001-2007}
    }
    
    Francis, D. & Meaney, M. Maternal care and the development of stress responses {1999} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {9}({1}), pp. {128-134} 
    article  
    Abstract: Studies dating from the 1950s have documented the impact of early life events on the development of behavioral and endocrine responses to stress. Recent findings suggest that these effects are mediated through changes in mother-offspring interactions and have identified central corticotropin-releasing factor systems as a critical target for the effects of variations in maternal care.
    BibTeX:
    @article{Francis1999,
      author = {Francis, DD and Meaney, MJ},
      title = {Maternal care and the development of stress responses},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      publisher = {CURRENT BIOLOGY LTD},
      year = {1999},
      volume = {9},
      number = {1},
      pages = {128-134}
    }
    
    FREMEAU, R., DUNCAN, G., FORNARETTO, M., DEARRY, A., GINGRICH, J., BREESE, G. & CARON, M. LOCALIZATION OF D1 DOPAMINE RECEPTOR MESSENGER-RNA IN BRAIN SUPPORTS A ROLE IN COGNITIVE, AFFECTIVE, AND NEUROENDOCRINE ASPECTS OF DOPAMINERGIC NEUROTRANSMISSION {1991} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {88}({9}), pp. {3772-3776} 
    article  
    Abstract: Expression of a D1 dopamine receptor was examined in the rat brain by using a combination of in situ hybridization and in vitro receptor autoradiography. Cells expressing D1 receptor mRNA were localized to many but not all, brain regions receiving dopaminergic innervation. The highest levels of hybridization were detected in the caudate-putamen, nucleus accumbens, and olfactory tubercle. Cells expressing D1 receptor mRNA were also detected throughout the cerebral cortex, limbic system, hypothalamus, and thalamus. D1 receptor mRNA was differentially expressed in distinct regions of the hippocampal formation. Dentate granule cells were labeled in dorsal but not ventral regions, whereas the subicular complex was prominently labeled in ventral but not dorsal regions. Intermediate to high levels of D1 binding sites, but no hybridizing D1 receptor mRNA, were detected in the substantia nigra pars reticulata, globus pallidus, entopeduncular nucleus, and subthalamic nucleus. In these brain regions, which are involved in the efferent flow of information from the basal ganglia, D1 receptors may be localized on afferent nerve terminals originating in other brain regions. These results indicate that in addition to a role in control of motor function, the D1 receptor may also participate in the cognitive, affective, and neuroendocrine effects of dopaminergic neurotransmission.
    BibTeX:
    @article{FREMEAU1991,
      author = {FREMEAU, RT and DUNCAN, GE and FORNARETTO, MG and DEARRY, A and GINGRICH, JA and BREESE, GR and CARON, MG},
      title = {LOCALIZATION OF D1 DOPAMINE RECEPTOR MESSENGER-RNA IN BRAIN SUPPORTS A ROLE IN COGNITIVE, AFFECTIVE, AND NEUROENDOCRINE ASPECTS OF DOPAMINERGIC NEUROTRANSMISSION},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1991},
      volume = {88},
      number = {9},
      pages = {3772-3776}
    }
    
    Gabrieli, J. Cognitive neuroscience of human memory {1998} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {49}, pp. {87-115} 
    article  
    Abstract: Current knowledge is summarized about long-term memory systems of the human brain, with memory systems defined as specific neural networks that support specific mnemonic processes. The summary integrates convergent evidence from neuropsychological studies of patients with brain lesions and from functional neuroimaging studies using positron emission tomography (PET) or functional magnetic resonance imaging (fMRI). Evidence is reviewed about the specific roles of hippocampal and parahippocampal regions, the amygdala, the basal ganglia, and various neocortical areas in declarative memory. Evidence is also reviewed about which brain regions mediate specific kinds of procedural memory, including sensorimotor, perceptual, and cognitive skill learning; perceptual and conceptual repetition priming; and several forms of conditioning. Findings are discussed in terms of the functional neural architecture of normal memory, age-related changes in memory performance, and neurological conditions that affect memory such as amnesia, Alzheimer's disease, Parkinson's disease, and Huntington's disease.
    BibTeX:
    @article{Gabrieli1998,
      author = {Gabrieli, JDE},
      title = {Cognitive neuroscience of human memory},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      publisher = {ANNUAL REVIEWS INC},
      year = {1998},
      volume = {49},
      pages = {87-115}
    }
    
    GAFFAN, D. SCENE-SPECIFIC MEMORY FOR OBJECTS - A MODEL OF EPISODIC MEMORY IMPAIRMENT IN MONKEYS WITH FORNIX TRANSECTION {1994} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {6}({4}), pp. {305-320} 
    article  
    Abstract: A series of five experiments investigated the relationship between object memory and scene memory in normal and fornix-transected monkeys. An algorithm created formally defined backgrounds and objects on a large visual display; the disposition of some particular objects in particular places in a particular background constitutes a formally defined scene. The animals learned four types of discrimination problem: (1) object-in-place discrimination learning, in which the correct (rewarded) response was to a particular object that always occupied the same place in a particular unique background, (2) place discrimination learning, in which the correct response was to a particular place in a unique background, with no distinctive object at that place, (3) object discrimination learning in unique backgrounds, in which the correct response was to a particular object that could occupy one or the other of two possible places in a unique background, and (4) object discrimination learning in varying backgrounds, in which the correct response was to a particular object that could appear at any place in any background. The severest impairment produced by fornix transection was in object-in-place learning. Fornix transection did not impair object discrimination learning in varying backgrounds. The results from the other two types of learning task showed intermediate severity of impair ment in the fornix-transected animals. The idea that fornix transection in the monkey impairs spatial memory but leaves object memory intact is thus shown to be an oversimplification The impairments of object memory in the present experiments are analogous to the impairments of episodic memory seen in human amnesic patients.
    BibTeX:
    @article{GAFFAN1994,
      author = {GAFFAN, D},
      title = {SCENE-SPECIFIC MEMORY FOR OBJECTS - A MODEL OF EPISODIC MEMORY IMPAIRMENT IN MONKEYS WITH FORNIX TRANSECTION},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      publisher = {MIT PRESS},
      year = {1994},
      volume = {6},
      number = {4},
      pages = {305-320}
    }
    
    Gallese, V., Keysers, C. & Rizzolatti, G. A unifying view of the basis of social cognition {2004} TRENDS IN COGNITIVE SCIENCES
    Vol. {8}({9}), pp. {396-403} 
    article DOI  
    Abstract: In this article we provide a unifying neural hypothesis on how individuals understand the actions and emotions of others. Our main claim is that the fundamental mechanism at the basis of the experiential understanding of others' actions is the activation of the mirror neuron system. A similar mechanism, but involving the activation of viscero-motor centers, underlies the experiential understanding of the emotions of others.
    BibTeX:
    @article{Gallese2004,
      author = {Gallese, V and Keysers, C and Rizzolatti, G},
      title = {A unifying view of the basis of social cognition},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {2004},
      volume = {8},
      number = {9},
      pages = {396-403},
      doi = {{10.1016/j.tics.2004.07.002}}
    }
    
    GARRIS, P. & WIGHTMAN, R. DIFFERENT KINETICS GOVERN DOPAMINERGIC TRANSMISSION IN THE AMYGDALA, PREFRONTAL CORTEX, AND STRIATUM - AN IN-VIVO VOLTAMMETRIC STUDY {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({1}), pp. {442-450} 
    article  
    Abstract: The regulation of extracellular dopamine (DA) concentrations was examined and compared in vivo in four projection fields of mesotelencephalic dopaminergic neurons with fast-scan cyclic voltammetry at carbon-fiber microelectrodes. Transient electrical stimulation of ascending DA fibers in a near physiological range of frequencies (10-20 Hz) elicited similar levels of extracellular DA in the medial prefrontal cortex (MPFC), basal lateral amygdaloid nucleus (BAN), caudate-putamen (CP), and nucleus accumbens (NAc) despite the documented 90-fold disparity in DA tissue levels and terminal density. However, marked differences were observed in the dynamics and overall frequency dependence of the evoked synaptic overflow of DA. These differences are due to the significantly different rates of release and uptake found in each of the four regions. For example, rate constants for the release and uptake of DA were similar in the MPFC and BAN but approximately 8 and 50 times less, respectively, than that in the CP and NAc. When the parameters were normalized to endogenous DA tissue content, a unique picture emerged: compared to all other regions, relative release was 10-fold greater in the MPFC while relative uptake was at least 10 times less in the BAN. The results further differentiate the functional characteristics of mesotelencephalic dopaminergic systems and demonstrate the regiospecific nature of DA neural transmission in the brain. In addition, the regulation of extracellular DA levels in the MPFC and BAN is suitable for the `'long-range'' transfer of chemical information in the brain and is consistent with a hypothesis of extrasynaptic neurotransmission.
    BibTeX:
    @article{GARRIS1994,
      author = {GARRIS, PA and WIGHTMAN, RM},
      title = {DIFFERENT KINETICS GOVERN DOPAMINERGIC TRANSMISSION IN THE AMYGDALA, PREFRONTAL CORTEX, AND STRIATUM - AN IN-VIVO VOLTAMMETRIC STUDY},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {1},
      pages = {442-450}
    }
    
    Giedd, J., Vaituzis, A., Hamburger, S., Lange, N., Rajapakse, J., Kaysen, D., Vauss, Y. & Rapoport, J. Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: Ages 4-18 years {1996} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {366}({2}), pp. {223-230} 
    article  
    Abstract: The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4-18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders. (C) 1996 Wiley-Liss, Inc.
    BibTeX:
    @article{Giedd1996,
      author = {Giedd, JN and Vaituzis, AC and Hamburger, SD and Lange, N and Rajapakse, JC and Kaysen, D and Vauss, YC and Rapoport, JL},
      title = {Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: Ages 4-18 years},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1996},
      volume = {366},
      number = {2},
      pages = {223-230}
    }
    
    Goldstein, J., Seidman, L., Horton, N., Makris, N., Kennedy, D., Caviness, V., Faraone, S. & Tsuang, M. Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging {2001} CEREBRAL CORTEX
    Vol. {11}({6}), pp. {490-497} 
    article  
    Abstract: The etiology and consistency of findings on normal sexual dimorphisms of the adult human brain are unresolved. In this study, we present a comprehensive evaluation of normal sexual dimorphisms of cortical and subcortical brain regions, using in vivo magnetic resonance imaging, in a community sample of 48 normal adults. The men and women were similar in age, education, ethnicity, socioeconomic status, general intelligence and handedness. Forty-five brain regions were assessed based on T-1-weighted three-dimensional images acquired from a 1.5 T magnet. Sexual dimorphisms of adult brain volumes were more evident in the cortex, with women having larger volumes, relative to cerebrum size, particularly in frontal and medial paralimbic cortices. Men had larger volumes, relative to cerebrum size, in frontomedial cortex, the amygdala and hypothalamus. A permutation test showed that, compared to other brain areas assessed in this study, there was greater sexual dimorphism among brain areas that are homologous with those identified in animal studies showing greater levels of sex steroid receptors during critical periods of brain development. These findings have implications for developmental studies that would directly test hypotheses about mechanisms relating sex steroid hormones to sexual dimorphisms in humans.
    BibTeX:
    @article{Goldstein2001,
      author = {Goldstein, JM and Seidman, LJ and Horton, NJ and Makris, N and Kennedy, DN and Caviness, VS and Faraone, SV and Tsuang, MT},
      title = {Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging},
      journal = {CEREBRAL CORTEX},
      publisher = {OXFORD UNIV PRESS INC},
      year = {2001},
      volume = {11},
      number = {6},
      pages = {490-497}
    }
    
    Good, C., Johnsrude, I., Ashburner, J., Henson, R., Friston, K. & Frackowiak, R. A voxel-based morphometric study of ageing in 465 normal adult human brains {2001} NEUROIMAGE
    Vol. {14}({1, Part 1}), pp. {21-36} 
    article DOI  
    Abstract: Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans. (C) 2001 Academic Press.
    BibTeX:
    @article{Good2001,
      author = {Good, CD and Johnsrude, IS and Ashburner, J and Henson, RNA and Friston, KJ and Frackowiak, RSJ},
      title = {A voxel-based morphometric study of ageing in 465 normal adult human brains},
      journal = {NEUROIMAGE},
      publisher = {ACADEMIC PRESS INC},
      year = {2001},
      volume = {14},
      number = {1, Part 1},
      pages = {21-36},
      doi = {{10.1006/nimg.2001.0786}}
    }
    
    Gorman, J., Kent, J., Sullivan, G. & Coplan, J. Neuroanatomical hypothesis of panic disorder, revised {2000} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {157}({4}), pp. {493-505} 
    article  
    Abstract: Objective: In a 1989 article, the authors provided a hypothesis for the neuroanatomical basis of panic disorder that attempted to explain why both medication and cognitive behavioral psychotherapy are effective treatments. Here they revise that hypothesis to consider developments in the preclinical understanding of the neurobiology of fear and avoidance. Method: The authors review recent literature on the phenomenology, neurobiology, and treatment of panic disorder and impressive developments in documenting the neuroanatomy of conditioned fear in animals. Results: There appears to be a remarkable similarity between the physiological and behavioral consequences of response to a conditioned fear stimulus and a panic attack. In animals, these responses are mediated by a ``fear network'' in the brain that is centered in the amygdala and involves its interaction with the hippocampus and medial prefrontal cortex. Projections from the amygdala to hypothalamic and brainstem sites explain many of the observed signs of conditioned fear responses. It is speculated that a similar network is involved in panic disorder. A convergence of evidence suggests that both heritable factors and stressful life events, particularly in early childhood, are responsible for the onset of panic disorder. Conclusions: Medications, particularly those that influence the serotonin system, are hypothesized to desensitize the fear network from the level of the amygdala through its projects to the hypothalamus and the brainstem. Effective psychosocial treatments may also reduce contextual fear and cognitive misattributions at the level of the prefrontal cortex and hippocampus. Neuroimaging studies should help clarify whether these hypotheses are correct.
    BibTeX:
    @article{Gorman2000,
      author = {Gorman, JM and Kent, JM and Sullivan, GM and Coplan, JD},
      title = {Neuroanatomical hypothesis of panic disorder, revised},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      publisher = {AMER PSYCHIATRIC PRESS, INC},
      year = {2000},
      volume = {157},
      number = {4},
      pages = {493-505}
    }
    
    Gottfried, J., O'Doherty, J. & Dolan, R. Encoding predictive reward value in human amygdala and orbitofrontal cortex {2003} SCIENCE
    Vol. {301}({5636}), pp. {1104-1107} 
    article  
    Abstract: Adaptive behavior is optimized in organisms that maintain flexible representations of the value of sensory-predictive cues. To identify central representations of predictive reward value in humans, we used reinforcer devaluation while measuring neural activity with functional magnetic resonance imaging. We presented two arbitrary visual stimuli, both before and after olfactory devaluation, in a paradigm of appetitive conditioning. In amygdala and orbitofrontal cortex, responses evoked by a predictive target stimulus were decreased after devaluation, whereas responses to the nondevalued stimulus were maintained. Thus, differential activity in amygdala and orbitofrontal cortex encodes the current value of reward representations accessible to predictive cues.
    BibTeX:
    @article{Gottfried2003,
      author = {Gottfried, JA and O'Doherty, J and Dolan, RJ},
      title = {Encoding predictive reward value in human amygdala and orbitofrontal cortex},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {2003},
      volume = {301},
      number = {5636},
      pages = {1104-1107}
    }
    
    Gotz, J., Chen, F., van Dorpe, J. & Nitsch, R. Formation of neurofibrillary tangles in P301L tau transgenic mice induced by A beta 42 fibrils {2001} SCIENCE
    Vol. {293}({5534}), pp. {1491-1495} 
    article  
    Abstract: beta -Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of beta -amyloid A beta (42) fibrils into the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neurons project to the injection sites. Gallyas silver impregnation identified NFTs that contained tau phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after A beta (42) injections. Our data support the hypothesis that A beta (42) fibrils can accelerate NFT formation in vivo.
    BibTeX:
    @article{Gotz2001,
      author = {Gotz, J and Chen, F and van Dorpe, J and Nitsch, RM},
      title = {Formation of neurofibrillary tangles in P301L tau transgenic mice induced by A beta 42 fibrils},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {2001},
      volume = {293},
      number = {5534},
      pages = {1491-1495}
    }
    
    Grace, A. Gating of information flow within the limbic system and the pathophysiology of schizophrenia {2000} BRAIN RESEARCH REVIEWS
    Vol. {31}({2-3}), pp. {330-341} 
    article  
    Abstract: Although first thought of as a dopaminergic disorder, there is little direct evidence to support a primary pathology in the dopamine system as the etiological factor in schizophrenia. In contrast, evidence is amassing in support of a cortical disturbance in this disorder; one consequence of which is a disruption in the cortical regulation of subcortical dopamine systems. Our studies show that the hippocampus plays a major role in this interaction, in that, along with the dopamine system, it provides a gating influence over information Row from the prefrontal cortex at the level of the nucleus accumbens. Moreover, chemically-induced disruption of the development of the hippocampus and entorhinal cortex were found to lead to pathophysiological changes in these interactions in the limbic system of adult rats. Therefore, schizophrenia is proposed to be a developmentally-related disorder, in which disruption of the hippocampal influence over the limbic system during ontogeny results in a pathological alteration of corticoaccumbens interactions in the adult organism. (C) 2000 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Grace2000,
      author = {Grace, AA},
      title = {Gating of information flow within the limbic system and the pathophysiology of schizophrenia},
      journal = {BRAIN RESEARCH REVIEWS},
      publisher = {ELSEVIER SCIENCE BV},
      year = {2000},
      volume = {31},
      number = {2-3},
      pages = {330-341},
      note = {Nobel Symposium 111: Schizophrenia - Pathophysiological Mechanisms, STOCKHOLM, SWEDEN, OCT 01-03, 1998}
    }
    
    Graeff, F., Guimaraes, F., DeAndrade, T. & Deakin, J. Role of 5-HT in stress, anxiety, and depression {1996} PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
    Vol. {54}({1}), pp. {129-141} 
    article  
    Abstract: There are conflicting results on the function of 5-HT in anxiety and depression. To reconcile this evidence, Deakin and Graeff have suggested that the ascending 5-HT pathway that originates in the dorsal raphe nucleus (DRN) and innervates the amygdala and frontal cortex facilitates conditioned fear, while the DRN-periventricular pathway innervating the periventricular and periaqueductal gray matter inhibits inborn fight/flight reactions to impending danger, pain, or asphyxia. To study the role of the DRN 5-HT system in anxiety, we microinjected 8-OH-DPAT into the DRN to inhibit 5 HT release. This treatment impaired inhibitory avoidance (conditioned fear) without affecting one-way escape (unconditioned fear) in the elevated T-maze, a new animal model of anxiety. We also applied three drug treatments that increase 5-HT release from DRN terminals: 1) intra-DRN microinjection of the benzodiazepine inverse agonist FG 4172, 2) intra-DRN microinjection of the excitatory amino acid kainic acid, and 3) intraperitoneal injection of the 5-HT releaser and uptake blocker D-fenfluramine. All treatments enhanced inhibitory avoidance in the T-maze. D-Fenfluramine and intra-DRN kainate also decreased one-way escape. In healthy volunteers, D-fenfluramine and the 5-HT agonist mCPP (mainly 5-HT2C) increased, while the antagonists ritanserin (5-HT2A/(2C)) and SR 46349B (5-HT2A) decreased skin conductance responses to an aversively conditioned stimulus (tone). In addition, D-fenfluramine decreased, whereas ritanserin increased subjective anxiety induced by simulated public speaking, thought to represent unconditioned anxiety. Overall, these results are compatible with the above hypothesis. Deakin and Graeff have suggested that the pathway connecting the median raphe nucleus (MRN) to the dorsal hippocampus promotes resistance to chronic, unavoidable stress. In the present study, we found that 24 h after electrolytic lesion of the rat MRN glandular gastric ulcers occurred, and the immune response to the mitogen concanavalin A was depressed. Seven days after the same lesion, the ulcerogenic effect of restraint was enhanced. Microinjection of 8-OH-DPAT, the nonselective agonist 5-MeO-DMT, or the 5-HT uptake inhibitor zimelidine into the dorsal hippocampus immediately after 2 h of restraint reversed the deficits of open arm exploration in the elevated plus-maze, measured 24 h after restraint. The effect of the two last drugs was antagonized by WAY-100135, a selective 5-HT1A receptor antagonist. These results are compatible with the hypothesis that the MRN-dorsal hippocampus 5-HT system attenuates stress by facilitation of hippocampal 5-HT1A-mediated neurotransmission. Clinical implications of these results are discussed, especially with regard to panic disorder and depression.
    BibTeX:
    @article{Graeff1996,
      author = {Graeff, FG and Guimaraes, FS and DeAndrade, TGCS and Deakin, JFW},
      title = {Role of 5-HT in stress, anxiety, and depression},
      journal = {PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1996},
      volume = {54},
      number = {1},
      pages = {129-141}
    }
    
    Grant, S., London, E., Newlin, D., Villemagne, V., Liu, X., Contoreggi, C., Phillips, R., Kimes, A. & Margolin, A. Activation of memory circuits during cue-elicited cocaine craving {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({21}), pp. {12040-12045} 
    article  
    Abstract: Evidence accumulated over more than 45 years has indicated that environmental stimuli can induce craving for drugs of abuse in individuals who have addictive disorders. However, the brain mechanisms that subserve such craving have not been elucidated. Here a positron emission tomographic study shows increased glucose metabolism in cortical and limbic regions implicated in several forms of memory when human volunteers who abuse cocaine are exposed to drug-related stimuli. Correlations of metabolic increases in the dorsolateral prefrontal cortex, medial temporal lobe (amygdala), and cerebellum with self-reports of craving suggest that a distributed neural network, which integrates emotional and cognitive aspects of memory, links environmental cues with cocaine craving.
    BibTeX:
    @article{Grant1996,
      author = {Grant, S and London, ED and Newlin, DB and Villemagne, VL and Liu, X and Contoreggi, C and Phillips, RL and Kimes, AS and Margolin, A},
      title = {Activation of memory circuits during cue-elicited cocaine craving},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1996},
      volume = {93},
      number = {21},
      pages = {12040-12045}
    }
    
    GRAY, J., FELDON, J., RAWLINS, J., SMITH, A. & HEMSLEY, D. THE NEUROPSYCHOLOGY OF SCHIZOPHRENIA {1991} BEHAVIORAL AND BRAIN SCIENCES
    Vol. {14}({1}), pp. {1-19} 
    article  
    Abstract: A model is proposed for integrating the neural and cognitive aspects of the positive symptoms of acute schizophrenia using evidence from: postmortem neuropathology and neurochemistry, clinical and preclinical studies of dopaminergic neurotransmission, anatomical connections between the limbic system and the basal ganglia, attentional and other cognitive abnormalities underlying the positive symptoms of schizophrenia, specific animal models of some of these abnormalities, and previous attempts to model the cognitive functions of the spetohippocampal system and the motor functions of the basal ganglia. Anatomically, the model emphasises the projections from the septohippocampal system, via the subiculum and the amygdala to nucleus accumbens and their interaction with the ascending dopaminergic projection to the accumbens. Psychologically, the model emphasizes a failure in schizophrenia to integrate stored memories of past regularieties of perceptual input with ongoing motor programs in the control of current perception. A number of recent experiments that offer support for the model are fully described, including anatomical studies of limbic-striatal connections, studies in the rat of the effects of damage to these connections and of the effects of amphetamine and neuroleptics on the partial reinforcement extinction effect, latent inhibition and the Kamin blocking effect, and studies of the latter two phenomena in acuate and chronic schizophrenics.
    BibTeX:
    @article{GRAY1991,
      author = {GRAY, JA and FELDON, J and RAWLINS, JNP and SMITH, AD and HEMSLEY, DR},
      title = {THE NEUROPSYCHOLOGY OF SCHIZOPHRENIA},
      journal = {BEHAVIORAL AND BRAIN SCIENCES},
      publisher = {CAMBRIDGE UNIV PRESS},
      year = {1991},
      volume = {14},
      number = {1},
      pages = {1-19}
    }
    
    GROENEWEGEN, H., BERENDSE, H., WOLTERS, J. & LOHMAN, A. THE ANATOMICAL RELATIONSHIP OF THE PREFRONTAL CORTEX WITH THE STRIATOPALLIDAL SYSTEM, THE THALAMUS AND THE AMYGDALA - EVIDENCE FOR A PARALLEL ORGANIZATION {1990} PROGRESS IN BRAIN RESEARCH
    Vol. {85}, pp. {95-118} 
    article  
    Abstract: Recent findings in primates indicate that the connections of the frontal lobe, the basal ganglia, and the thalamus are organized in a number of parallel, functionally segregated circuits. In the present account, we have focused on the organization of the connections between the prefrontal cortex, the basal ganglia and the mediodorsal thalamic nucleus in the rat. It is concluded that in this species, in analogy with the situation in primates, a number of parallel basal ganglia-thalamocortical circuits exist. Furthermore, data are presented indicating that the projections from particular parts of the amygdala and from individual nuclei of he midline and intralaminar thalamic complex to the prefrontal cortex and the striatum are in register with the arrangements in the parallel circuits. These findings emphasize that the functions of the different subregions of the prefrontal cortex cannot be considered separately but must be viewed as components of the integrative functions of the circuits in which they are involved.
    BibTeX:
    @article{GROENEWEGEN1990,
      author = {GROENEWEGEN, HJ and BERENDSE, HW and WOLTERS, JG and LOHMAN, AHM},
      title = {THE ANATOMICAL RELATIONSHIP OF THE PREFRONTAL CORTEX WITH THE STRIATOPALLIDAL SYSTEM, THE THALAMUS AND THE AMYGDALA - EVIDENCE FOR A PARALLEL ORGANIZATION},
      journal = {PROGRESS IN BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1990},
      volume = {85},
      pages = {95-118}
    }
    
    Gurvits, T., Shenton, M., Hokama, H., Ohta, H., Lasko, N., Gilbertson, M., Orr, S., Kikinis, R., Jolesz, F., McCarley, R. & Pitman, R. Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder {1996} BIOLOGICAL PSYCHIATRY
    Vol. {40}({11}), pp. {1091-1099} 
    article  
    Abstract: This study used quantitative volumetric magnetic resonance imaging techniques to explore the neuroanatomic correlates of chronic, combat-related posttraumatic stress disorder (PTSD) in seven Vietnam veterans with PTSD compared with seven nonPTSD combat veterans and eight normal nonveterans. Both left and right hippocampi were significantly smaller in the PTSD subjects compared to the Combat Control and Normal subjects, even after adjusting for age, whole brain volume, and lifetime alcohol consumption. There were no statistically significant group differences in intracranial cavity, whole brain, ventricles, ventricle:brain ratio, or amygdala. Subarachnoidal cerebrospinal fluid was increased in both veteran groups, Our finding of decreased hippocampal volume in PTSD subjects is consistent with results of other investigations which utilized only trauma-unexposed central groups, Hippocampal volume was directly correlated with combat exposure, which suggests that traumatic stress may damage the hippocampus. Alternatively, smaller hippocampi volume may lay be a pre-existing risk factor for combat exposure and/or the development of PTSD upon combat exposure. (C) 1996 Society of Biological Psychiatry
    BibTeX:
    @article{Gurvits1996,
      author = {Gurvits, TV and Shenton, ME and Hokama, H and Ohta, H and Lasko, NB and Gilbertson, MW and Orr, SP and Kikinis, R and Jolesz, FA and McCarley, RW and Pitman, RK},
      title = {Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1996},
      volume = {40},
      number = {11},
      pages = {1091-1099}
    }
    
    HALGREN, E., SQUIRES, N., WILSON, C., ROHRBAUGH, J., BABB, T. & CRANDALL, P. ENDOGENOUS POTENTIALS GENERATED IN THE HUMAN HIPPOCAMPAL-FORMATION AND AMYGDALA BY INFREQUENT EVENTS {1980} SCIENCE
    Vol. {210}({4471}), pp. {803-805} 
    article  
    BibTeX:
    @article{HALGREN1980,
      author = {HALGREN, E and SQUIRES, NK and WILSON, CL and ROHRBAUGH, JW and BABB, TL and CRANDALL, PH},
      title = {ENDOGENOUS POTENTIALS GENERATED IN THE HUMAN HIPPOCAMPAL-FORMATION AND AMYGDALA BY INFREQUENT EVENTS},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {1980},
      volume = {210},
      number = {4471},
      pages = {803-805}
    }
    
    HALGREN, E., WALTER, R., CHERLOW, D. & CRANDALL, P. MENTAL PHENOMENA EVOKED BY ELECTRICAL-STIMULATION OF HUMAN HIPPOCAMPAL FORMATION AND AMYGDALA {1978} BRAIN
    Vol. {101}({MAR}), pp. {83-117} 
    article  
    BibTeX:
    @article{HALGREN1978,
      author = {HALGREN, E and WALTER, RD and CHERLOW, DG and CRANDALL, PH},
      title = {MENTAL PHENOMENA EVOKED BY ELECTRICAL-STIMULATION OF HUMAN HIPPOCAMPAL FORMATION AND AMYGDALA},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {1978},
      volume = {101},
      number = {MAR},
      pages = {83-117}
    }
    
    Hamann, S., Ely, T., Grafton, S. & Kilts, C. Amygdala activity related to enhanced memory for pleasant and aversive stimuli {1999} NATURE NEUROSCIENCE
    Vol. {2}({3}), pp. {289-293} 
    article  
    Abstract: Pleasant or aversive events are better remembered than neutral events. Emotional enhancement of episodic memory has been linked to the amygdala in animal and neuropsychological studies. Using positron emission tomography, we show that bilateral amygdala activity during memory encoding is correlated with enhanced episodic recognition memory for both pleasant and aversive visual stimuli relative to neutral stimuli, and that this relationship is specific to emotional stimuli. Furthermore, data suggest that the amygdala enhances episodic memory in part through modulation of hippocampal activity The human amygdala seems to modulate the strength of conscious memory for events according to emotional importance, regardless of whether the emotion is pleasant or aversive.
    BibTeX:
    @article{Hamann1999,
      author = {Hamann, SB and Ely, TD and Grafton, ST and Kilts, CD},
      title = {Amygdala activity related to enhanced memory for pleasant and aversive stimuli},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {1999},
      volume = {2},
      number = {3},
      pages = {289-293}
    }
    
    Hariri, A., Bookheimer, S. & Mazziotta, J. Modulating emotional responses: effects of a neocortical network on the limbic system {2000} NEUROREPORT
    Vol. {11}({1}), pp. {43-48} 
    article  
    Abstract: Humans share with animals a primitive neural system for processing emotions such as fear and anger. Unlike other animals, humans have the unique ability to control and modulate instinctive emotional reactions through intellectual processes such as reasoning, rationalizing, and labeling our experiences. This study used functional MRI to identify the neural networks underlying this ability. Subjects either matched the affect of one of two faces to that of a simultaneously presented target face (a perceptual task) or identified the affect of a target face by choosing one of two simultaneously presented linguistic labels (an intellectual task). Matching angry or frightened expressions was associated with increased regional cerebral blood flow (rCBF) in the left and right amygdala, the brain's primary fear centers. Labeling these same expressions was associated with a diminished rCBF response in the amygdalae. This decrease correlated with a simultaneous increase in rCBF in the right prefrontal cortex, a neocortical region implicated in regulating emotional responses. These results provide evidence for a network in which higher regions attenuate emotional responses at the most fundamental levels in the brain and suggest a neural basis for modulating emotional experience through interpretation and labeling. NeuroReport 11:43-48 (C) 2000 Lippincott Williams & Williams.
    BibTeX:
    @article{Hariri2000,
      author = {Hariri, AR and Bookheimer, SY and Mazziotta, JC},
      title = {Modulating emotional responses: effects of a neocortical network on the limbic system},
      journal = {NEUROREPORT},
      publisher = {LIPPINCOTT WILLIAMS & WILKINS},
      year = {2000},
      volume = {11},
      number = {1},
      pages = {43-48}
    }
    
    Hariri, A., Drabant, E., Munoz, K., Kolachana, L., Mattay, V., Egan, M. & Weinberger, D. A susceptibility gene for affective disorders and the response of the human amygdala {2005} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {62}({2}), pp. {146-152} 
    article  
    Abstract: Background: A common regulatory variant (5-HTTLPR) in the human serotonin transporter gene (SLC6A4), resulting in altered transcription and transporter availability, has been associated with vulnerability for affective disorders, including anxiety and depression. A recent functional magnetic resonance imaging study suggested that this association may be mediated by 5-HTTLPR effects on the response bias of the human amygdala-a brain region critical for emotional and social behavior-to environmental threat. Objectives and Design: To examine the effects of 5-HTTLPR genotype on the reactivity of the human amygdala to salient environmental cues with functional magnetic resonance imaging in a large (N = 92) cohort of volunteers carefully screened for past and present medical or psychiatric illness, and to explore the effects of 5-HTTLPR genotype as well as amygdala reactivity on harm avoidance, a putative personality measure related to trait anxiety. Results: We now confirm the finding of 5-HTTLPR short allele-driven amygdala hyperreactivity in a large independent cohort of healthy subjects with no history of psychiatric illness or treatment. Furthermore, we demonstrate that these genotype effects on amygdala function are consistent with a dominant short allele effect and are equally prominent in men and women. However, neither 5-HTTLPR genotype, amygdala reactivity, nor genotype-driven Variability in this reactivity was reflected in harm avoidance scores. Conclusions: Our results reveal a potent modulatory effect of the 5-HTTLPR on amygdala reactivity to environmental threat. Since this genetically driven effect exists in healthy subjects, it does not, in and of itself, predict dimensions of mood or temperament. As such, the 5-HTTLPR may represent a classic susceptibility factor for affective disorders by biasing the functional reactivity of the human amygdala in the context of stressful life experiences and/or deficient cortical regulatory input.
    BibTeX:
    @article{Hariri2005,
      author = {Hariri, AR and Drabant, EM and Munoz, KE and Kolachana, LS and Mattay, VS and Egan, MF and Weinberger, DR},
      title = {A susceptibility gene for affective disorders and the response of the human amygdala},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      publisher = {AMER MEDICAL ASSOC},
      year = {2005},
      volume = {62},
      number = {2},
      pages = {146-152}
    }
    
    Hariri, A., Goldberg, T., Mattay, V., Kolachana, B., Callicott, J., Egan, M. & Weinberger, D. Brain-derived neurotrophic factor val(66)met polymorphism affects human memory-related hippocampal activity and predicts memory performance {2003} JOURNAL OF NEUROSCIENCE
    Vol. {23}({17}), pp. {6690-6694} 
    article  
    Abstract: BDNF plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus. A frequent single nucleotide polymorphism in the targeting region of the human BDNF gene (val (66)met) has been associated with abnormal intracellular trafficking and regulated secretion of BDNF in cultured hippocampal neurons transfected with the met allele. In addition, the met allele has been associated with abnormal hippocampal neuronal function as well as impaired episodic memory in human subjects, but a direct effect of BDNF alleles on hippocampal processing of memory has not been demonstrated. We studied the relationship of the BDNF val (66)met genotype and hippocampal activity during episodic memory processing using blood oxygenation level-dependent functional magnetic resonance imaging and a declarative memory task in healthy individuals. Met carriers exhibited relatively diminished hippocampal engagement in comparison with val homozygotes during both encoding and retrieval processes. Remarkably, the interaction between the BDNF val (66)met genotype and the hippocampal response during encoding accounted for 25% of the total variation in recognition memory performance. These data implicate a specific genetic mechanism for substantial normal variation in human declarative memory and suggest that the basic effects of BDNF signaling on hippocampal function in experimental animals are important in humans.
    BibTeX:
    @article{Hariri2003,
      author = {Hariri, AR and Goldberg, TE and Mattay, VS and Kolachana, BS and Callicott, JH and Egan, MF and Weinberger, DR},
      title = {Brain-derived neurotrophic factor val(66)met polymorphism affects human memory-related hippocampal activity and predicts memory performance},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2003},
      volume = {23},
      number = {17},
      pages = {6690-6694}
    }
    
    Hariri, A., Mattay, V., Tessitore, A., Fera, F. & Weinberger, D. Neocortical modulation of the amygdala response to fearful stimuli {2003} BIOLOGICAL PSYCHIATRY
    Vol. {53}({6}), pp. {494-501} 
    article DOI  
    Abstract: Background: The cortical circuitry involved in conscious cognitive processes and the subcortical circuitry involved in fear responses have been extensively studied with neuroimaging, but their interactions remain largely unexplored. A recent functional magnetic resonance imaging (fMRI) study demonstrated that the engagement of the right prefrontal cortex during the cognitive evaluation of angry and fearful facial expressions is associated with an attenuation of the response of the amygdala to these same stimuli, providing evidence for a functional neural network for emotional regulation. Methods: In the current study, we have explored the generalizability of this functional network by using threatening and fearful non-face stimuli derived from the International Affective Picture System (IAPS), as well as the influence of this network on peripheral autonomic responses. Results: Similar to the earlier findings with facial expressions, blood oxygen level dependent fMRI revealed that whereas perceptual processing of IAPS stimuli was associated with a bilateral amygdala response, cognitive evaluation of these same stimuli was associated with attenuation of this amygdala response and a correlated increase in response of the right prefrontal cortex and the anterior cingulate cortex. Moreover, this pattern was reflected in changes in skin conductance. Conclusions: The current results further implicate the importance of neocortical regions, including the prefrontal and anterior cingulate cortices, in regulating emotional responses mediated by the amygdala through conscious evaluation and appraisal. (C) 2003 Society of Biological Psychiatry.
    BibTeX:
    @article{Hariri2003a,
      author = {Hariri, AR and Mattay, VS and Tessitore, A and Fera, F and Weinberger, DR},
      title = {Neocortical modulation of the amygdala response to fearful stimuli},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2003},
      volume = {53},
      number = {6},
      pages = {494-501},
      doi = {{10.1016/S0002-3223(03)01786-9}}
    }
    
    Hariri, A., Mattay, V., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., Egan, M. & Weinberger, D. Serotonin transporter genetic variation and the response of the human amygdala {2002} SCIENCE
    Vol. {297}({5580}), pp. {400-403} 
    article  
    Abstract: A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin [5-hydroxytryptamine, (5-HT)] function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.
    BibTeX:
    @article{Hariri2002,
      author = {Hariri, AR and Mattay, VS and Tessitore, A and Kolachana, B and Fera, F and Goldman, D and Egan, MF and Weinberger, DR},
      title = {Serotonin transporter genetic variation and the response of the human amygdala},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {2002},
      volume = {297},
      number = {5580},
      pages = {400-403}
    }
    
    Hatfield, T., Han, J., Conley, M., Gallagher, M. & Holland, P. Neurotoxic lesions of basolateral, but not central, amygdala interfere with pavlovian second-order conditioning and reinforcer devaluation effects {1996} JOURNAL OF NEUROSCIENCE
    Vol. {16}({16}), pp. {5256-5265} 
    article  
    Abstract: Considerable evidence suggests that various discrete nuclei within the amygdala complex are critically involved in the assignment of emotional significance or value to events through associative learning. Much of this evidence comes from aversive conditioning procedures. For example, lesions of either basolateral amygdala (ABL) or the central nucleus (CN) interfere with the acquisition or expression of conditioned fear. The present study examined the effects of selective neurotoxic lesions of either ABL or CN on the acquisition of positive incentive value by a conditioned stimulus (CS) with two appetitive Pavlovian conditioning procedures. In second-order conditioning experiments, rats first received light-food pairings intended to endow the light with reinforcing power. The acquired reinforcing power of the light was then measured by examining its ability to serve as a reinforcer for second-order conditioning of a tone when tone-light pairings were given in the absence of food. Acquisition of second-order conditioning was impaired in rats with ASL lesions but not in rats with CN lesions. In reinforcer devaluation procedures, conditioned responding of rats with ABL lesions was insensitive to postconditioning changes in the value of the reinforcer, whereas rats with CN lesions, like normal rats, were able to spontaneously adjust their CRs to the current value of the reinforcer. The results of both test procedures indicate that ABL, but not CN, is part of a system involved in CSs' acquisition of positive incentive value. Together with evidence that identifies a role for CN in certain changes in attentional processing of CSs in conditioning, these results suggest that separate amygdala subsystems contribute to a variety of processes inherent in associative learning.
    BibTeX:
    @article{Hatfield1996,
      author = {Hatfield, T and Han, JS and Conley, M and Gallagher, M and Holland, P},
      title = {Neurotoxic lesions of basolateral, but not central, amygdala interfere with pavlovian second-order conditioning and reinforcer devaluation effects},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1996},
      volume = {16},
      number = {16},
      pages = {5256-5265}
    }
    
    Haxby, J., Hoffman, E. & Gobbini, M. Human neural systems for face recognition and social communication {2002} BIOLOGICAL PSYCHIATRY
    Vol. {51}({1}), pp. {59-67} 
    article  
    Abstract: Face perception is mediated by a distributed neural system in humans that consists of multiple, bilateral regions. The functional organization of this system embodies a distinction between the representation of invariant aspects of faces, which is the basis for recognizing individuals, and the representation of changeable aspects, such as eye gaze, expression, and lip movement, which underlies the perception of information that facilitates social communication. The system also has a hierarchical organization. A core system, consisting of occipitotemporal regions in extrastriate visual cortex, mediates the visual analysis of faces. An extended system consists of regions from neural systems for other cognitive functions that can act in concert with the core system to extract meaning from faces. Of regions in the extended system for face perception, the amygdala plays a central role in processing the social relevance of information gleaned from faces, particularly when that information may signal a potential threat. (C) 2002 Society of Biological Psychiatry.
    BibTeX:
    @article{Haxby2002,
      author = {Haxby, JV and Hoffman, EA and Gobbini, MI},
      title = {Human neural systems for face recognition and social communication},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2002},
      volume = {51},
      number = {1},
      pages = {59-67}
    }
    
    Haxby, J., Hoffman, E. & Gobbini, M. The distributed human neural system for face perception {2000} TRENDS IN COGNITIVE SCIENCES
    Vol. {4}({6}), pp. {223-233} 
    article  
    Abstract: Face perception, perhaps the most highly developed visual skill in humans, is mediated by a distributed neural system in humans that is comprised of multiple, bilateral regions. We propose a model for the organization of this system that emphasizes a distinction between the representation of invariant and changeable aspects of faces. The representation of invariant aspects of faces underlies the recognition of individuals, whereas the representation of changeable aspects of faces, such as eye gaze, expression, and lip movement, underlies the perception of information that facilitates social communication. The model is also hierarchical insofar as it is divided into a core system extended system. The core system is comprised of occipitotemporal regions in visual cortex that mediate the visual analysis of faces. In the core system, the representation of invariant aspects is mediated more by the face-responsive region fusiform gyrus, whereas the representation of changeable aspects is mediated more by the face-responsive region in the superior temporal sulcus. The extended system is comprised of regions from neural systems for other cognitive functions that, can be recruited to act in concert with the regions in the core system to extract meaning from faces.
    BibTeX:
    @article{Haxby2000,
      author = {Haxby, JV and Hoffman, EA and Gobbini, MI},
      title = {The distributed human neural system for face perception},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {2000},
      volume = {4},
      number = {6},
      pages = {223-233}
    }
    
    HECKERS, S., OHTAKE, T., WILEY, R., LAPPI, D., GEULA, C. & MESULAM, M. COMPLETE AND SELECTIVE CHOLINERGIC DENERVATION OF RAT NEOCORTEX AND HIPPOCAMPUS BUT NOT AMYGDALA BY AN IMMUNOTOXIN AGAINST THE P75 NGF RECEPTOR {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({3, Part 1}), pp. {1271-1289} 
    article  
    Abstract: The immunotoxin 192 IgG-saporin, produced by coupling the ribosome-inactivating protein saporin to the monoclonal 192 IgG antibody against the low-affinity p75 NGF receptor (NGFr), was injected into the cerebral ventricle, septal area, and substantia innominata of adult rats. Injections into the cerebral ventricle induced a complete loss of NGFr-positive basal forebrain neurons and their axons. Extensive loss of cholinergic neurons was found in the septum, diagonal band, and magnocellular preoptic nucleus but not in the nucleus basalis-substantia innominata complex, where many cholinergic, presumably NGFr-negative, neurons remained intact. Cholinergic fibers were completely lost in the neocortex and hippocampus, showed some preservation in allocortical areas, and showed only minor loss in the amygdala. The NGFr-positive cholinergic basal forebrain neurons progressively degenerated during the first 5 d and did not recover after 180 d. The effect of intraventricular 192 IgG-saporin injections on NGFr-positive basal forebrain neurons could be blocked by simultaneous intraventricular injection of colchicine. Intraparenchymal injections into the septal area or substantia innominata damaged cholinergic neurons mainly around the injection sites and reduced their respective cortical and hippocampal projections. Noncholinergic septal neurons containing parvalbumin and noncholinergic neurons containing calbindin-D-28K or NADPHd, which were adjacent to cholinergic nucleus basalis-substantia innominata neurons, were not affected by 192 IgG-saporin. The ChAT immunoreactivity in cortical interneurons, habenula, and brainstem was unchanged. Dopaminergic and noradrenergic cortical afferents remained intact. 192 IgG-saporin damaged two neuronal groups outside the basal forebrain that express the p75 NGF receptor: NGFr-positive cerebellar Purkinje cells after intraventricular injection and cholinergic striatal interneurons after injections into the substantia innominata. These results indicate that the immunotoxin 192 IgG-saporin induces a complete and selective lesion of NGFr-positive cholinergic basal forebrain neurons projecting to hippocampus and neocortex.
    BibTeX:
    @article{HECKERS1994,
      author = {HECKERS, S and OHTAKE, T and WILEY, RG and LAPPI, DA and GEULA, C and MESULAM, MM},
      title = {COMPLETE AND SELECTIVE CHOLINERGIC DENERVATION OF RAT NEOCORTEX AND HIPPOCAMPUS BUT NOT AMYGDALA BY AN IMMUNOTOXIN AGAINST THE P75 NGF RECEPTOR},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {3, Part 1},
      pages = {1271-1289}
    }
    
    HEILIG, M., KOOB, G., EKMAN, R. & BRITTON, K. CORTICOTROPIN-RELEASING FACTOR AND NEUROPEPTIDE-Y - ROLE IN EMOTIONAL INTEGRATION {1994} TRENDS IN NEUROSCIENCES
    Vol. {17}({2}), pp. {80-85} 
    article  
    Abstract: The amygdala complex integrates stressful stimuli and is critical in transducing their aversive value into autonomic, endocrine and behavioural responses. Stimulation within the amygdala complex produces signs of fear without a relevant external object, while lesions in this region abolish normal fear responses. In a manner characteristic of phylogenetically old limbic brain areas, the complex neurochemical anatomy of the amygdala involves a large number of phylogenetically old peptide mediators. The distribution and connectivity of these peptide systems have been extensively studied, but less is known about their functional role. Recent evidence suggests that two neuropeptides, corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) exert a reciprocal regulation of responsiveness to stressful stimuli, possibly via an interaction of these two systems in the amygdala.
    BibTeX:
    @article{HEILIG1994,
      author = {HEILIG, M and KOOB, GF and EKMAN, R and BRITTON, KT},
      title = {CORTICOTROPIN-RELEASING FACTOR AND NEUROPEPTIDE-Y - ROLE IN EMOTIONAL INTEGRATION},
      journal = {TRENDS IN NEUROSCIENCES},
      publisher = {ELSEVIER SCI LTD},
      year = {1994},
      volume = {17},
      number = {2},
      pages = {80-85}
    }
    
    HEILIG, M., MCLEOD, S., BROT, M., HEINRICHS, S., MENZAGHI, F., KOOB, G. & BRITTON, K. ANXIOLYTIC-LIKE ACTION OF NEUROPEPTIDE-Y - MEDIATION BY Y1 RECEPTORS IN AMYGDALA, AND DISSOCIATION FROM FOOD-INTAKE EFFECTS {1993} NEUROPSYCHOPHARMACOLOGY
    Vol. {8}({4}), pp. {357-363} 
    article  
    Abstract: Evidence from animal and human studies suggests that neuropeptide Y (NPY) may be a potent endogenous anxiolytic. The anatomic structures mediating this action of the peptide remain unknown. Furthermore, in addition to its anxiolytic-like effects, intracerebroventricular administration of NPY induces food intake through hypothalamic mechanisms, making the anxiolytic-like action of the peptide more difficult to interpret. The purpose of this study was to examine the anatomic substrate for the effects of NPY on anxiety, and to characterize the NPY receptors mediating these effects. Intracerebroventricular injection of NPY produced increased food intake in free-feeding animals, and dose-dependent anticonflict/anxiolytic-like effects in an established animal model of anxiety, the Geller-Seifter punished responding test. In contrast, microinjection of NPY into the central nucleus of the amygdala did not increase food intake in free-feeding animals, did not affect unpunished lever pressing for food, but did reproduce the anticonflict/anxiolytic-like effect with high potency. The selective NPY-Y1 agonist, p[Leu31,Pro34]NPY was approximately equipotent with native NPY in the conflict paradigm, and markedly more potent than the Y2 agonist, NPY13-36. Intrastriatal injections had no effect on conflict behavior. Thus, activation of Y1 receptors in the central nucleus of the amygdala produces effects similar to established anxiolytics without affecting food intake, suggesting that Y1-receptors in the amygdala may be a substrate for anxiolytic actions of NPY.
    BibTeX:
    @article{HEILIG1993,
      author = {HEILIG, M and MCLEOD, S and BROT, M and HEINRICHS, SC and MENZAGHI, F and KOOB, GF and BRITTON, KT},
      title = {ANXIOLYTIC-LIKE ACTION OF NEUROPEPTIDE-Y - MEDIATION BY Y1 RECEPTORS IN AMYGDALA, AND DISSOCIATION FROM FOOD-INTAKE EFFECTS},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1993},
      volume = {8},
      number = {4},
      pages = {357-363}
    }
    
    HEIMER, L., ZAHM, D., CHURCHILL, L., KALIVAS, P. & WOHLTMANN, C. SPECIFICITY IN THE PROJECTION PATTERNS OF ACCUMBAL CORE AND SHELL IN THE RAT {1991} NEUROSCIENCE
    Vol. {41}({1}), pp. {89-125} 
    article  
    Abstract: The efferent projections of the core and shell areas of the nucleus accumbens were studied with a combination of anterograde and retrograde tract-tracing methods, including Phaseolus vulgaris-leucoagglutinin, horseradish peroxidase and fluorescent tracers. Both the core and shell regions project to pallidal areas, i.e. ventral pallidum and entopeduncular nucleus, with a distinct topography in the sense that the core projection is located in the dorsolateral part of ventral pallidum, whereas the shell projects to the medial part of the subcommissural ventral pallidum. Both regions of the accumbens also project to mesencephalon with a bias for the core projection to innervate the substantia nigra-lateral mesencephalic tegmentum, and for the shell projection to reach primarily the ventral tegmental-paramedian tegmentum area. The most pronounced differences between core and shell projections exist in regard to the hypothalamus and extended amygdala. Whereas the core projects primarily to the entopeduncular nucleus including a part that invades the lateral hypothalamus, the shell, in addition, projects diffusely throughout the rostrocaudal extent of the lateral hypothalamus as well as to the extended amygdala, especially its sublenticular part. Both the core and shell of the accumbens have unmistakable striatal characteristics both histologically and in their connectional patterns. The shell, however, has additional features that are reminiscent of the recently described extended amygdala [Alheid G. F. and Heimer L. (1988) Neuroscience 27, 1-39; de Olmos J. S. et al. (1985) In The Rat Nervous System, pp. 223-334]; in fact, the possibility exists that the shell represents a transitional zone that seems to characterize most of the fringes of the striatal complex, where it adjoins the extended amygdala.
    BibTeX:
    @article{HEIMER1991,
      author = {HEIMER, L and ZAHM, DS and CHURCHILL, L and KALIVAS, PW and WOHLTMANN, C},
      title = {SPECIFICITY IN THE PROJECTION PATTERNS OF ACCUMBAL CORE AND SHELL IN THE RAT},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1991},
      volume = {41},
      number = {1},
      pages = {89-125}
    }
    
    HEINRICHS, S., PICH, E., MICZEK, K., BRITTON, K. & KOOB, G. CORTICOTROPIN-RELEASING FACTOR ANTAGONIST REDUCES EMOTIONALITY IN SOCIALLY DEFEATED RATS VIA DIRECT NEUROTROPIC ACTION {1992} BRAIN RESEARCH
    Vol. {581}({2}), pp. {190-197} 
    article  
    Abstract: Introduction of a socially naive male rat into the home territory of a resident counterpart results in agonistic interactions, leading to the rapid social defeat of the intruder. Exposure to the aggressive resident produces a stress-response profile consisting of neuroendocrine activation and coping behaviors such as submission. The present studies examined the dependence of these adaptive responses on endogenous brain Corticotropin-Releasing Factor (CRF), a peptide hormone known to coordinate neuronally mediated- and pituitary-adrenal responses to stress. The Elevated Plus-Maze was employed as an animal model of emotionality in which stressors reduce subsequent exploration of open maze arms without walls in favor of enclosed maze arms. A CRF antagonist, alpha-hel CRF9-41, administered intracerebroventricularly (5 and 25-mu-g i.c.v.) immediately post-stress and 5 min prior to maze testing reversed the heightened emotionality produced by the resident exposure stressor. This action paralleled that of an anxiolytic dose of the short-acting benzodiazepine, midazolam (1.5 mg/kg i.p.). Intraamygdaloid administration of lower doses of the CRF antagonist (125, 250 and 500 ng i.c.) also reversed, dose-dependently, the effect of exposure to an aggressive resident without altering the behavior of unstressed control animals. Further, the enhanced release of ACTH and corticosterone following social conflict was not modified over the short term by the intra-amygdaloid dose of CRF antagonist (250 ng i.c.) which was effective in reversing stress-induced hyper-emotionality. These results suggest that limbic system CRF substrates exert an anxiogenic effect on the exploratory behavior of socially defeated rats via a pituitary-adrenal-independent mechanism.
    BibTeX:
    @article{HEINRICHS1992,
      author = {HEINRICHS, SC and PICH, EM and MICZEK, KA and BRITTON, KT and KOOB, GF},
      title = {CORTICOTROPIN-RELEASING FACTOR ANTAGONIST REDUCES EMOTIONALITY IN SOCIALLY DEFEATED RATS VIA DIRECT NEUROTROPIC ACTION},
      journal = {BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1992},
      volume = {581},
      number = {2},
      pages = {190-197}
    }
    
    Heinz, A., Braus, D., Smolka, M., Wrase, J., Puls, I., Hermann, D., Klein, S., Grusser, S., Flor, H., Schumann, G., Mann, K. & Buchel, C. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter {2005} NATURE NEUROSCIENCE
    Vol. {8}({1}), pp. {20-21} 
    article DOI  
    Abstract: Major depression is conditionally linked to a polymorphism of the human serotonin transporter gene (SLC6A4). During the presentation of aversive, but not pleasant, pictures, healthy carriers of the SLC6A4 short (s) allele showed stronger activation of the amygdala on functional magnetic resonance imaging. s carriers also showed greater coupling between the amygdala and the ventromedial prefrontal cortex, which may contribute to the abnormally high activity in the amygdala and medial prefrontal cortex seen in major depression.
    BibTeX:
    @article{Heinz2005,
      author = {Heinz, A and Braus, DF and Smolka, MN and Wrase, J and Puls, I and Hermann, D and Klein, S and Grusser, SM and Flor, H and Schumann, G and Mann, K and Buchel, C},
      title = {Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2005},
      volume = {8},
      number = {1},
      pages = {20-21},
      doi = {{10.1038/nn1366}}
    }
    
    Herman, J., Figueiredo, H., Mueller, N., Ulrich-Lai, Y., Ostrander, M., Choi, D. & Cullinan, W. Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness {2003} FRONTIERS IN NEUROENDOCRINOLOGY
    Vol. {24}({3}), pp. {151-180} 
    article DOI  
    Abstract: Appropriate regulatory control of the hypothatamo-pituitary-adrenocortical stress axis is essential to health and survival. The following review documents the principle extrinsic and intrinsic mechanisms responsible for regulating stress-responsive CRH neurons of the hypothalamic paraventricular nucleus, which summate excitatory and inhibitory inputs into a net secretory signal at the pituitary gland. Regions that directly innervate these neurons are primed to relay sensory information, including visceral afferents, nociceptors and circumventricular organs, thereby promoting `reactive' corticosteroid responses to emergent homeostatic challenges. Indirect inputs from the limbic-associated structures are capable of activating these same cells in the absence of frank physiological challenges; such `anticipatory' signals regulate glucocorticoid release under conditions in which physical challenges may be predicted, either by innate programs or conditioned stimuli. Importantly, `anticipatory' circuits are integrated with neural pathways subserving `reactive' responses at multiple levels. The resultant hierarchical organization of stress-responsive neurocircuitries is capable of comparing information from multiple limbic sources with internally generated and peripherally sensed information, thereby tuning the relative activity of the adrenal cortex. Imbalances among these limbic pathways and homeostatic sensors are likely to underlie hypothalamo-pituitary adrenocortical dysfunction associated with numerous disease processes. (C) 2003 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Herman2003,
      author = {Herman, JP and Figueiredo, H and Mueller, NK and Ulrich-Lai, Y and Ostrander, MM and Choi, DC and Cullinan, WE},
      title = {Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness},
      journal = {FRONTIERS IN NEUROENDOCRINOLOGY},
      publisher = {ACADEMIC PRESS INC ELSEVIER SCIENCE},
      year = {2003},
      volume = {24},
      number = {3},
      pages = {151-180},
      doi = {{10.1016/j.yfrne.2003.07.001}}
    }
    
    HERZOG, A. & VANHOESEN, G. TEMPORAL NEOCORTICAL AFFERENT CONNECTIONS TO AMYGDALA IN RHESUS-MONKEY {1976} BRAIN RESEARCH
    Vol. {115}({1}), pp. {57-69} 
    article  
    BibTeX:
    @article{HERZOG1976,
      author = {HERZOG, AG and VANHOESEN, GW},
      title = {TEMPORAL NEOCORTICAL AFFERENT CONNECTIONS TO AMYGDALA IN RHESUS-MONKEY},
      journal = {BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1976},
      volume = {115},
      number = {1},
      pages = {57-69}
    }
    
    HITCHCOCK, J. & DAVIS, M. LESIONS OF THE AMYGDALA, BUT NOT OF THE CEREBELLUM OR RED NUCLEUS, BLOCK CONDITIONED FEAR AS MEASURED WITH THE POTENTIATED STARTLE PARADIGM {1986} BEHAVIORAL NEUROSCIENCE
    Vol. {100}({1}), pp. {11-\&} 
    article  
    BibTeX:
    @article{HITCHCOCK1986,
      author = {HITCHCOCK, J and DAVIS, M},
      title = {LESIONS OF THE AMYGDALA, BUT NOT OF THE CEREBELLUM OR RED NUCLEUS, BLOCK CONDITIONED FEAR AS MEASURED WITH THE POTENTIATED STARTLE PARADIGM},
      journal = {BEHAVIORAL NEUROSCIENCE},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1986},
      volume = {100},
      number = {1},
      pages = {11-&}
    }
    
    Hoffman, E. & Haxby, J. Distinct representations of eye gaze and identity in the distributed human neural system for face perception {2000} NATURE NEUROSCIENCE
    Vol. {3}({1}), pp. {80-84} 
    article  
    Abstract: Face perception requires representation of invariant aspects that underlie identity recognition as well as representation of changeable aspects, such as eye gaze and expression, that facilitate social communication. Using functional magnetic resonance imaging (fMRI), we investigated the perception of face identity and eye gaze in the human brain. Perception of face identity was mediated more by regions in the inferior occipital and fusiform gyri, and perception of eye gaze was mediated more by regions in the superior temporal sulci. Eye-gaze perception also seemed to recruit the spatial cognition system in the intraparietal sulcus to encode the direction of another's gate and to focus attention in that direction.
    BibTeX:
    @article{Hoffman2000,
      author = {Hoffman, EA and Haxby, JV},
      title = {Distinct representations of eye gaze and identity in the distributed human neural system for face perception},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {2000},
      volume = {3},
      number = {1},
      pages = {80-84}
    }
    
    Holland, P. & Gallagher, M. Amygdala circuitry in attentional and representational processes {1999} TRENDS IN COGNITIVE SCIENCES
    Vol. {3}({2}), pp. {65-73} 
    article  
    Abstract: The amygdala has long been implicated in the display of emotional behavior and emotional information processing, especially in the context of aversive events. In this review, we discuss recent evidence that links the amygdala to several aspects of food- motivated associative learning, including functions often characterized as attention, reinforcement and representation, Each of these functions depends on the operation of separate amygdalar subsystems, through their connections with other brain systems. Notably, very different processing systems seem to be mediated by the central nucleus and basolateral amygdala, subregions of the amygdala that differ in their anatomy and in their connectivity. The basolateral amygdala is involved in the acquisition and representation of reinforcement value, apparently through its connections with ventral striatal dopamine systems and with the orbitofrontal cortex. The dentral nucleus, however,contributes heavily to attentional function in conditioning, by way of its influence on basal forebrain cholinergic systems and on the dorsolateral striatum.
    BibTeX:
    @article{Holland1999,
      author = {Holland, PC and Gallagher, M},
      title = {Amygdala circuitry in attentional and representational processes},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {1999},
      volume = {3},
      number = {2},
      pages = {65-73}
    }
    
    Hu, X., Lipsky, R., Zhu, G., Akhtar, L., Taubman, J., Greenberg, B., Xu, K., Arnold, P., Richter, M., Kennedy, J., Murphy, D. & Goldman, D. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder {2006} AMERICAN JOURNAL OF HUMAN GENETICS
    Vol. {78}({5}), pp. {815-826} 
    article  
    Abstract: A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The L-G allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed co-dominant allele action and low, nearly equivalent expression for the S and L-G alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function LALA genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The L-A allele was twofold overtransmitted to the patients with OCD. The HTTLPR LALA genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.
    BibTeX:
    @article{Hu2006,
      author = {Hu, XZ and Lipsky, RH and Zhu, GS and Akhtar, LA and Taubman, J and Greenberg, BD and Xu, K and Arnold, PD and Richter, MA and Kennedy, JL and Murphy, DL and Goldman, D},
      title = {Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder},
      journal = {AMERICAN JOURNAL OF HUMAN GENETICS},
      publisher = {UNIV CHICAGO PRESS},
      year = {2006},
      volume = {78},
      number = {5},
      pages = {815-826}
    }
    
    HURLEY, K., HERBERT, H., MOGA, M. & SAPER, C. EFFERENT PROJECTIONS OF THE INFRALIMBIC CORTEX OF THE RAT {1991} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {308}({2}), pp. {249-276} 
    article  
    Abstract: On the basis of stimulation studies, it has been proposed that the infralimbic cortex (ILC), Brodmann area 25, may serve as an autonomic motor cortex. To explore this hypothesis, we have combined anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde tracing with wheat germ aggutinin conjugated to horseradish peroxidase (WGA-HRP) to determine the efferent projections from the ILC. Axons exit the ILC in one of three efferent pathways. The dorsal pathway ascends through layers III and V to innervate the prelimbic and anterior cingulate cortices. The lateral pathway courses through the nucleus accumbens to innervate the insular cortex, the perirhinal cortex, and parts of the piriform cortex. In addition, some fibers from the lateral pathway enter the corticospinal tract. The ventral pathway is by far the largest and innervates the thalamus (including the paraventricular nucleus of the thalamus, the border zone between the paraventricular and medial dorsal nuclei, and the paratenial, reuniens, ventromedial, parafasicular, and subparafasicular nuclei), the hypothalamus (including the lateral hypothalamic and medial preoptic areas, and the suprachiasmatic, dorsomedial, and supramammillary nuclei), the amygdala (including the central, medial, and basomedial nuclei, and the periamygdaloid cortex) and the bed nucleus of the stria terminalis. The ventral efferent pathway also provides descending projections to autonomic cell groups of the brainstem and spinal cord including the periaqueductal gray matter, the parabrachial nucleus, the nucleus of the solitary tract, the dorsal motor vagal nucleus, the nucleus ambiguus, and the ventrolateral medulla, as well as lamina I and the intermediolateral column of the spinal cord. The ILC has extensive projections to central autonomic nuclei that may subserve a role in modulating visceral responses to emotional stimuli, such as stress.
    BibTeX:
    @article{HURLEY1991,
      author = {HURLEY, KM and HERBERT, H and MOGA, MM and SAPER, CB},
      title = {EFFERENT PROJECTIONS OF THE INFRALIMBIC CORTEX OF THE RAT},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1991},
      volume = {308},
      number = {2},
      pages = {249-276}
    }
    
    Impey, S., Smith, D., Obrietan, K., Donahue, R., Wade, C. & Storm, D. Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning {1998} NATURE NEUROSCIENCE
    Vol. {1}({7}), pp. {595-601} 
    article  
    Abstract: Recent studies suggest that the CREB-CRE transcriptional pathway is pivotal in the formation of some types of long-term memory. However, it has not been demonstrated that stimuli that induce learning and memory activate CRE-mediated gene expression. To address this issue, we used a mouse strain transgenic for a CRE-lac Z reporter to examine the effects of hippocampus-dependent learning on CRE-mediated gene expression in the brain. Training for contextual conditioning or passive avoidance led to significant increases in CRE-dependent gene expression in areas CA1 and CA3 of the hippocampus. Auditory cue fear-conditioning, which is amygdala dependent, was associated with increased CRE-mediated gene expression in the amygdala, but not the hippocampus. These data demonstrate that learning in response to behavioral conditioning activates the CRE transcriptional pathway in specific areas of brain.
    BibTeX:
    @article{Impey1998,
      author = {Impey, S and Smith, DM and Obrietan, K and Donahue, R and Wade, C and Storm, DR},
      title = {Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {1998},
      volume = {1},
      number = {7},
      pages = {595-601}
    }
    
    INSEL, T. OXYTOCIN - A NEUROPEPTIDE FOR AFFILIATION - EVIDENCE FROM BEHAVIORAL, RECEPTOR AUTORADIOGRAPHIC, AND COMPARATIVE-STUDIES {1992} PSYCHONEUROENDOCRINOLOGY
    Vol. {17}({1}), pp. {3-35} 
    article  
    Abstract: Oxytocin (OT) is a nine amino acid peptide synthesized in hypothalamic cells which project either to the neurohypophysis or to sites within the central nervous system. Although neurohypophyseal OT release has long been associated with uterine contraction and milk ejection, the function of intracerebral OT remains unclear. On the basis of behavioral, cellular, and comparative studies, this review suggests that brain OT influences the formation of social bonds. The first-part of this review examines evidence linking central OT to several forms of affiliation. Central administration of OT induces maternal and reproductive behaviors in rats primed with gonadal steroids. OT antagonists and hypothalamic lesions block the initiation of maternal and reproductive behaviors but have no effects on these behaviors once established. Our new studies in rat pups demonstrate that central OT selectively decreases the separation response, an effect which mimics social contact. These studies of parental, reproductive, and attachment behaviors suggest that exogenous OT has ``prosocial'' effects and that endogenous OT may be essential for initiating social interaction. In a second series of experiments, we investigated the cellular mechanisms for OT's effects on social behavior by means of autoradiographic receptor binding. In the rat forebrain, OT receptors are expressed in several limbic regions believed to be involved in the integration of sensory processing. The regulation of these receptors is surprisingly resistant to either ablation of OT cells or repeated central administration of OT. However, receptors in two regions, the bed nucleus of the stria terminalis (BNST) and the ventromedial nucleus of the hypothalamus (VMN), appear selectively induced by exogenous or endogenous increases in gonadal steroids. At parturition, binding to OT receptors increases 84% in the BNST, and at estrus, binding increases 35% in the VMN. These results demonstrate that physiologic changes in gonadal steroids can alter receptor expression in anatomically discrete target fields and thereby direct responsiveness to endogenous neuropeptide release. A model for OT's effects on social behavior is proposed, which relies on the heterologous regulation of the brain OT receptor. A third series of experiments tested the hypothesis that brain OT influences affiliation by comparing prairie and montane voles, two closely related species with dichotomous systems of social organization. Although no differences appear in the presynaptic expression of the neuropeptide, OT receptors are distributed in complementary patterns in the two species. In the highly affiliative prairie vole, receptors are most evident in the BNST and one of its primary afferents, the lateral amygdala, highlighting a circuit previously implicated in maternal behavior. In the asocial montane vole, receptors are absent in these regions. At parturition, when the female montane vole first manifests maternal.behavior, the expression of OT receptors changes in the direction of the pattern observed in the highly parental prairie vole. The specificity of these findings is supported by (1) studies in other species with similar behavioral differences and (2) the failure to find concurrent species differences in the distribution of receptors for several other neurotransmitters. These various behavioral, receptor autoradiographic, and comparative studies all provide evidence that brain OT systems, via alterations in receptor number and distribution, may influence the expression of social behavior. As OT is an exclusively mammalian neuropeptide, this central neuroendocrine system may have evolved relatively recently to promote selective aspects of social bond formation.
    BibTeX:
    @article{INSEL1992a,
      author = {INSEL, TR},
      title = {OXYTOCIN - A NEUROPEPTIDE FOR AFFILIATION - EVIDENCE FROM BEHAVIORAL, RECEPTOR AUTORADIOGRAPHIC, AND COMPARATIVE-STUDIES},
      journal = {PSYCHONEUROENDOCRINOLOGY},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1992},
      volume = {17},
      number = {1},
      pages = {3-35}
    }
    
    INSEL, T. & SHAPIRO, L. OXYTOCIN RECEPTOR DISTRIBUTION REFLECTS SOCIAL-ORGANIZATION IN MONOGAMOUS AND POLYGAMOUS VOLES {1992} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {89}({13}), pp. {5981-5985} 
    article  
    Abstract: The neuropeptide oxytocin has been implicated in the mediation of several forms of affiliative behavior including parental care, grooming, and sex behavior. Here we demonstrate that species from the genus Microtus (voles) selected for differences in social affiliation show contrasting patterns of oxytocin receptor expression in brain. By in vitro receptor autoradiography with an iodinated oxytocin analogue, specific binding to brain oxytocin receptors was observed in both the monogamous prairie vole (Microtus ochrogaster) and the polygamous montane vole (Microtus montanus). In the prairie vole, oxytocin receptor density was highest in the prelimbic cortex, bed nucleus of the stria terminalis, nucleus accumbens, midline nuclei of the thalamus, and the lateral aspects of the amygdala. These brain areas showed little binding in the montane vole, in which oxytocin receptors were localized to the lateral septum, ventromedial nucleus of the hypothalamus, and cortical nucleus of the amygdala. Similar differences in brain oxytocin receptor distribution were observed in two additional species, the monogamous pine vole (Microtus pinetorum) and the polygamous meadow vole (Microtus pennsylvanicus). Receptor distributions for two other neurotransmitter systems implicated in the mediation of social behavior, benzodiazepines, and mu-opioids did not show comparable species differences. Furthermore, in the montane vole, which shows little affiliative behavior except during the postpartum period, brain oxytocin receptor distribution changed within 24 hr of parturition, concurrent with the onset of maternal behavior. We suggest that variable expression of the oxytocin receptor in brain may be an important mechanism in evolution of species-typical differences in social bonding and affiliative behavior.
    BibTeX:
    @article{INSEL1992,
      author = {INSEL, TR and SHAPIRO, LE},
      title = {OXYTOCIN RECEPTOR DISTRIBUTION REFLECTS SOCIAL-ORGANIZATION IN MONOGAMOUS AND POLYGAMOUS VOLES},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD PRESS},
      year = {1992},
      volume = {89},
      number = {13},
      pages = {5981-5985}
    }
    
    ISACKSON, P., HUNTSMAN, M., MURRAY, K. & GALL, C. BDNF MESSENGER-RNA EXPRESSION IS INCREASED IN ADULT-RAT FOREBRAIN AFTER LIMBIC SEIZURES - TEMPORAL PATTERNS OF INDUCTION DISTINCT FROM NGF {1991} NEURON
    Vol. {6}({6}), pp. {937-948} 
    article  
    Abstract: We have localized brain-derived neurotrophic factor (BDNF) mRNA in rat brain and examined its regulation by seizure activity. In situ hybridization of BDNF S-35-cRNA most prominently labeled neurons in hippocampal stratum pyramidale and stratum granulosum, superficial olfactory cortex, pyramidal cell layers of neocortex, amygdala, claustrum, endopiriform nucleus, anterior olfactory nucleus, and ventromedial hypothalamus. Hybridization to BDNF mRNA was markedly increased in all of these regions after lesion-induced recurrent limbic seizures and within dentate gyrus granule cells following one electrically stimulated epileptiform afterdischarge. In contrast to seizure-elicited changes in nerve growth factor (NGF) mRNA expression, increases in BDNF mRNA occur in a greater number of different neuronal populations and develop several hours more rapidly in extrahippocampal loci. These results indicate that regulation by physiological activity may be an intrinsic property of this class of neurotrophic factor but that, in the recurrent seizure paradigm, different mechanisms mediate increased expression of mRNAs for BDNF and NGF outside hippocampus.
    BibTeX:
    @article{ISACKSON1991,
      author = {ISACKSON, PJ and HUNTSMAN, MM and MURRAY, KD and GALL, CM},
      title = {BDNF MESSENGER-RNA EXPRESSION IS INCREASED IN ADULT-RAT FOREBRAIN AFTER LIMBIC SEIZURES - TEMPORAL PATTERNS OF INDUCTION DISTINCT FROM NGF},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {1991},
      volume = {6},
      number = {6},
      pages = {937-948}
    }
    
    Iversen, L. Cannabis and the brain {2003} BRAIN
    Vol. {126}({Part 6}), pp. {1252-1270} 
    article DOI  
    Abstract: The active compound in herbal cannabis, Delta(9)-tetrahydrocannabinol, exerts all of its known central effects through the CB1 cannabinoid receptor. Research on cannabinoid mechanisms has been facilitated by the availability of selective antagonists acting at CB1 receptors and the generation of CB1 receptor knockout mice. Particularly important classes of neurons that express high levels of CB1 receptors are GABAergic interneurons in hippocampus, amygdala and cerebral cortex, which also contain the neuropeptides cholecystokinin. Activation of CB1 receptors leads to inhibition of the release of amino acid and monoamine neurotransmitters. The lipid derivatives anandamide and 2-arachidonylglycerol act as endogenous ligands for CB1 receptors (endocannabinoids). They may act as retrograde synaptic mediators of the phenomena of depolarization-induced suppression of inhibition or excitation in hippocampus and cerebellum. Central effects of cannabinoids include disruption of psychomotor behaviour, short-term memory impairment, intoxication, stimulation of appetite, antinociceptive actions (particularly against pain of neuropathic origin) and anti-emetic effects. Although there are signs of mild cognitive impairment in chronic cannabis users there is little evidence that such impairments are irreversible, or that they are accompanied by drug-induced neuropathology. A proportion of regular users of cannabis develop tolerance and dependence on the drug. Some studies have linked chronic use of cannabis with an increased risk of psychiatric illness, but there is little evidence for any causal link. The potential medical applications of cannabis in the treatment of painful muscle spasms and other symptoms of multiple sclerosis are currently being tested in clinical trials. Medicines based on drugs that enhance the function of endocannabinoids may offer novel therapeutic approaches in the future.
    BibTeX:
    @article{Iversen2003,
      author = {Iversen, L},
      title = {Cannabis and the brain},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {2003},
      volume = {126},
      number = {Part 6},
      pages = {1252-1270},
      doi = {{10.1093/brain/awg143}}
    }
    
    IZQUIERDO, I., DA CUNHA, C., ROSAT, R., JERUSALINSKY, D., FERREIRA, M. & MEDINA, J. NEUROTRANSMITTER RECEPTORS INVOLVED IN POST-TRAINING MEMORY PROCESSING BY THE AMYGDALA, MEDIAL SEPTUM, AND HIPPOCAMPUS OF THE RAT {1992} BEHAVIORAL AND NEURAL BIOLOGY
    Vol. {58}({1}), pp. {16-26} 
    article  
    BibTeX:
    @article{IZQUIERDO1992,
      author = {IZQUIERDO, I and DA CUNHA, C and ROSAT, R and JERUSALINSKY, D and FERREIRA, MBC and MEDINA, JH},
      title = {NEUROTRANSMITTER RECEPTORS INVOLVED IN POST-TRAINING MEMORY PROCESSING BY THE AMYGDALA, MEDIAL SEPTUM, AND HIPPOCAMPUS OF THE RAT},
      journal = {BEHAVIORAL AND NEURAL BIOLOGY},
      publisher = {ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS},
      year = {1992},
      volume = {58},
      number = {1},
      pages = {16-26}
    }
    
    Izquierdo, I. & Medina, J. Memory formation: The sequence of biochemical events in the hippocampus and its connection to activity in other brain structures {1997} NEUROBIOLOGY OF LEARNING AND MEMORY
    Vol. {68}({3}), pp. {285-316} 
    article  
    Abstract: Recent data have demonstrated a biochemical sequence of events in the rat hippocampus that is necessary for memory formation of inhibitory avoidance behavior. The sequence initially involves the activation of three different types of glutamate receptors followed by changes in second messengers and biochemical cascades led by enhanced activity of protein kinases A, C, and G and calcium-calmodulin protein kinase II, followed by changes in glutamate receptor subunits and binding properties and increased expression of constitutive and inducible transcription factors. The biochemical events are regulated early after training by hormonal and neurohumoral mechanisms related to alertness, anxiety, and stress, and 3-6 h after training by pathways related to mood and affect. The early modulation is mediated locally by GABAergic, cholinergic, and noradrenergic synapses and by putative retrograde synaptic messengers, and extrinsically by the amygdala and possibly the medial septum, which handle emotional components of memories and are direct or indirect sites of action for several hormones and neurotransmitters. The late modulation relies on dopamine D-1, beta-noradrenergic, and 5HT1A receptors in the hippocampus and dopaminergic, noradrenergic, and serotoninergic pathways. Evidence indicates that hippocampal activity mediated by glutamate AMPA receptors must persist during at least 3 h after training in order for memories to be consolidated. Probably, this activity is transmitted to other areas, including the source of the dopaminergic, noradrenergic, and serotoninergic pathways, and the entorhinal and posterior parietal cortex. The entorhinal and posterior parietal cortex participate in memory consolidation minutes after the hippocampal chain of events starts, in both cases through glutamate NMDA receptor-mediated processes, and their intervention is necessary in order to complete memory consolidation. The hippocampus, amygdala, entorhinal cortex, and parietal cortex are involved in retrieval in the first few days after training; at 30 days from training only the entorhinal and parietal cortex are involved, and at 60 days only the parietal cortex is necessary for retrieval. Based on observations on other forms of hippocampal plasticity and on memory formation in the chick brain, it is suggested that the hippocampal chain of events that underlies memory formation is linked to long-term storage elsewhere through activity-dependent changes in cell connectivity. (C) 1997 Academic Press.
    BibTeX:
    @article{Izquierdo1997,
      author = {Izquierdo, I and Medina, JH},
      title = {Memory formation: The sequence of biochemical events in the hippocampus and its connection to activity in other brain structures},
      journal = {NEUROBIOLOGY OF LEARNING AND MEMORY},
      publisher = {ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS},
      year = {1997},
      volume = {68},
      number = {3},
      pages = {285-316}
    }
    
    Jack, C., Petersen, R., Xu, Y., Waring, S., OBrien, P., Tangalos, E., Smith, G., Ivnik, R. & Kokmen, E. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease {1997} NEUROLOGY
    Vol. {49}({3}), pp. {786-794} 
    article  
    Abstract: Magnetic resonance imaging (MRI)-based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly control subjects and patients with Alzheimer's disease (AD) of moderate to advanced severity. In terms of clinical utility, however, a more important issue concerns the ability of the technique to differentiate between normal elderly control subjects and AD patients with the very mildest form of the disease. We performed MRI-based volumetric measurements of the hippocampus, parahippocampal gyrus, and amygdala in 126 cognitively normal elderly control subjects and 94 patients with probable AD. The diagnosis of BD was made according to NINDS/ADRDA criteria, and disease severity was categorized by Clinical Dementia Rating (CDR) scores. Patients with CDR 0.5 were classified as very mild, CDR 1 as mild, and CDR 2 as moderate disease severity. Volumes of each structure declined with increasing age in control subjects and did so in parallel for men and women. The volume of each measured MTL structure also declined with age in patients with AD. The volume of each MTL structure was significantly smaller in AD patients than control subjects (p < 0.001). Of the several MTL measures, the total hippocampal volumetric measurements were best at discriminating control subjects from AD patients. The mean hippocampal volumes for AD patients relative to control subjects by severity of disease were as follows: very mild AD (CDR 0.5) -1.75 SD below the control mean, mild AD (CDR 1) -1.99 SD, and moderate AD (CDR 2) -2.22 SD, Age- and gender-adjusted, normalized MRI-based hippocampal volumetric measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process.
    BibTeX:
    @article{Jack1997,
      author = {Jack, CR and Petersen, RC and Xu, YC and Waring, SC and OBrien, PC and Tangalos, EG and Smith, GE and Ivnik, RJ and Kokmen, E},
      title = {Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease},
      journal = {NEUROLOGY},
      publisher = {LIPPINCOTT-RAVEN PUBL},
      year = {1997},
      volume = {49},
      number = {3},
      pages = {786-794}
    }
    
    Jentsch, J. & Taylor, J. Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli {1999} PSYCHOPHARMACOLOGY
    Vol. {146}({4}), pp. {373-390} 
    article  
    Abstract: Drug abuse and dependence define behavioral states involving increased allocation of behavior towards drug seeking and taking at the expense of more appropriate behavioral patterns. As such. addiction can be viewed as increased control of behavior by the desired drug (due to its unconditioned, rewarding properties). It is also clear that drug-associated (conditioned) stimuli acquire heightened abilities to control behaviors. These phenomena have been linked with dopamine function within the ventral striatum and amygdala and have been described specifically in terms of motivational and incentive learning processes. New data are emerging that suggest that regions of the frontal cortex involved in inhibitory response control are directly affected by long-term exposure to drugs of abuse. The result of chronic drug use may be frontal cortical cognitive dysfunction, resulting in an inability to inhibit inappropriate unconditioned or conditioned responses elicited by drugs, by related stimuli or by internal drive states. Drug-seeking behavior may thus be due to two related phenomena: (1) augmented incentive motivational qualities of the drug and associated stimuli (due to limbic/amygdalar dysfunction) and (2) impaired inhibitory control (due to frontal cortical dysfunction). In this review, we consider the neuro-anatomical and neurochemical substrates subserving inhibitory control and motivational processes in the rodent and primate brain and their putative impact on drug seeking. The evidence for cognitive impulsivity in drug abuse associated with dysfunction of the frontostriatal system will be discussed, and an integrative hypothesis for compulsive reward-seeking in drug abuse will be presented.
    BibTeX:
    @article{Jentsch1999,
      author = {Jentsch, JD and Taylor, JR},
      title = {Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli},
      journal = {PSYCHOPHARMACOLOGY},
      publisher = {SPRINGER VERLAG},
      year = {1999},
      volume = {146},
      number = {4},
      pages = {373-390}
    }
    
    Johnson, A. & Thunhorst, R. The neuroendocrinology of thirst and salt appetite: Visceral sensory signals and mechanisms of central integration {1997} FRONTIERS IN NEUROENDOCRINOLOGY
    Vol. {18}({3}), pp. {292-353} 
    article  
    Abstract: This review examines recent advances in the study of the behavioral responses to deficits of body water and body sodium that in humans are accompanied by the sensations of thirst and salt appetite. Thirst and salt appetite are satisfied by ingesting water and salty substances. These behavioral responses to losses of body fluids, together with reflex endocrine and neural responses, are critical for reestablishing homeostasis. Like their endocrine and neural counterparts, these behaviors are under the control of both excitatory and inhibitory influences arising from changes in osmolality, endocrine factors such as angiotensin and aldosterone, and neural signals from low and high pressure baroreceptors. The excitatory and inhibitory influences reaching the brain require the integrative capacity of a neural network which includes the structures of the lamina terminalis, the amygdala, the perifornical area, and the paraventricular nucleus in the forebrain, and the lateral parabrachial nucleus (LPBN), the nucleus tractus solitarius (NTS), and the area postrema in the hindbrain. These regions are discussed in terms of their roles in receiving afferent sensory input and in processing information related to hydromineral balance. Osmoreceptors controlling thirst are located in systemic viscera and in central structures that lack the blood-brain barrier. Angiotensin and aldosterone act on and through structures of the lamina terminalis and the amygdala to stimulate thirst and sodium appetite under conditions of hypovolemia. The NTS and LPBN receive neural signals from baroreceptors and are responsible for inhibiting the ingestion of fluids under conditions of increased volume and pressure and for stimulating thirst under conditions of hypovolemia and hypotension. The interplay of multiple facilitory influences within the brain may take the form of interactions between descending angiotensinergic systems originating in the forebrain and ascending adrenergic systems emanating from the hindbrain. Oxytocin and serotonin are additional candidate neurochemicals with postulated inhibitory central actions and with essential roles in the overall integration of sensory input within the neural network devoted to maintaining hydromineral balance. (C) 1997 Academic Press.
    BibTeX:
    @article{Johnson1997,
      author = {Johnson, AK and Thunhorst, RL},
      title = {The neuroendocrinology of thirst and salt appetite: Visceral sensory signals and mechanisms of central integration},
      journal = {FRONTIERS IN NEUROENDOCRINOLOGY},
      publisher = {ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS},
      year = {1997},
      volume = {18},
      number = {3},
      pages = {292-353}
    }
    
    KALIVAS, P. & ALESDATTER, J. INVOLVEMENT OF N-METHYL-D-ASPARTATE RECEPTOR STIMULATION IN THE VENTRAL TEGMENTAL AREA AND AMYGDALA IN BEHAVIORAL SENSITIZATION TO COCAINE {1993} JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
    Vol. {267}({1}), pp. {486-495} 
    article  
    Abstract: Systemic administration of N-methyl-D-aspartate (NMDA) antagonists prevents the development of behavioral sensitization to amphetamine-like psychostimulants. Pretreatment with the non-competitive NMDA antagonist, MK-801, resulted in a dose-dependent blockade of behavioral sensitization to cocaine. However, pretreatment with the highest dose of MK-801 (0.25 mg/kg i.p.) alone inhibited the behavioral response to a subsequent cocaine challenge 24 hr later. The induction of behavioral sensitization is known to result, at least partly, from an action by psychostimulants in the ventral tegmental area (VTA). To determine wheter the dose-dependent inhibition of behavioral sensitization to cocaine by NMDA antagonists resulted from receptor blockade in the VTA, rats were pretreated in the VTA with the MK-801 or the competitive NMDA antagonist, 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid, before systemically administered cocaine (30 mg/kg i.p.). Two to 3 days later rats were challenged with cocaine alone (1 5 mg/kg i. p.). Pretreatment with either NMDA antagonist into the VTA prevented the manifestation of behavioral sensitization. Intracranial pretreatment with MK-801 was also made into the nucleus accumbens and amygdala which have been implicated in psychostimulant-induced sensitization. Whereas MK-801 was without effect in the nucleus accumbens, when microinjected into the ventral amygdala it prevented the manifestation of behavioral sensitization to a cocaine challenge. The blockade of sensitization by MK-801 in the VTA was produced with a minimum effective dose of 0.01 nmol, whereas the minimum effective dose in the amygdala was 1.0 nmol. These data demonstrate that stimulation of NMDA receptors in the VTA and amygdala is necessary in the development of behavioral sensitization to cocaine.
    BibTeX:
    @article{KALIVAS1993,
      author = {KALIVAS, PW and ALESDATTER, JE},
      title = {INVOLVEMENT OF N-METHYL-D-ASPARTATE RECEPTOR STIMULATION IN THE VENTRAL TEGMENTAL AREA AND AMYGDALA IN BEHAVIORAL SENSITIZATION TO COCAINE},
      journal = {JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS},
      publisher = {WILLIAMS & WILKINS},
      year = {1993},
      volume = {267},
      number = {1},
      pages = {486-495}
    }
    
    Kalivas, P. & Volkow, N. The neural basis of addiction: A pathology of motivation and choice {2005} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {162}({8}), pp. {1403-1413} 
    article  
    Abstract: Objective: A primary behavioral pathology in drug addiction is the overpowering motivational strength and decreased ability to control the desire to obtain drugs. In this review the authors explore how advances in neurobiology are approaching an understanding of the cellular and circuitry underpinnings of addiction, and they describe the novel pharmacotherapeutic targets emerging from this understanding. Method: Findings from neuroimaging of addicts are integrated with cellular studies in animal models of drug seeking. Results: While dopamine is critical for acute reward and initiation of addiction, end-stage addiction results primarily from cellular adaptations in anterior cingulate and orbitofrontal glutamatergic projections to the nucleus accumbens. Pathophysiological plasticity in excitatory transmission reduces the capacity of the prefrontal cortex to initiate behaviors in response to biological rewards and to provide executive control over drug seeking. Simultaneously, the prefrontal cortex is hyperresponsive to stimuli predicting drug availability, resulting in supraphysiological glutamatergic drive in the nucleus accumbens, where excitatory synapses have a reduced capacity to regulate neurotransmission. Conclusions: Cellular adaptations in prefrontal glutamatergic innervation of the accumbens promote the compulsive character of drug seeking in addicts by decreasing the value of natural rewards, diminishing cognitive control ( choice), and enhancing glutamatergic drive in response to drug-associated stimuli.
    BibTeX:
    @article{Kalivas2005,
      author = {Kalivas, PW and Volkow, ND},
      title = {The neural basis of addiction: A pathology of motivation and choice},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      publisher = {AMER PSYCHIATRIC PUBLISHING, INC},
      year = {2005},
      volume = {162},
      number = {8},
      pages = {1403-1413},
      note = {157th Annual Meeting of the American-Psychiatric-Association, New York, NY, MAY 01-06, 2004}
    }
    
    KAPP, B., FRYSINGER, R., GALLAGHER, M. & HASELTON, J. AMYGDALA CENTRAL NUCLEUS LESIONS - EFFECT ON HEART-RATE CONDITIONING IN THE RABBIT {1979} PHYSIOLOGY & BEHAVIOR
    Vol. {23}({6}), pp. {1109-1117} 
    article  
    BibTeX:
    @article{KAPP1979,
      author = {KAPP, BS and FRYSINGER, RC and GALLAGHER, M and HASELTON, JR},
      title = {AMYGDALA CENTRAL NUCLEUS LESIONS - EFFECT ON HEART-RATE CONDITIONING IN THE RABBIT},
      journal = {PHYSIOLOGY & BEHAVIOR},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1979},
      volume = {23},
      number = {6},
      pages = {1109-1117}
    }
    
    Kaufmann, W., Worley, P., Pegg, J., Bremer, M. & Isakson, P. COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({6}), pp. {2317-2321} 
    article  
    Abstract: Postnatal development and adult function of the central nervous system are dependent on the capacity of neurons to effect long-term changes of specific properties in response to neural activity, This neuronal response has been demonstrated to be tightly correlated with the expression of a set of regulatory genes which include transcription factors as well as molecules that can directly modify cellular signaling, it is hypothesized that these proteins play a role in activity-dependent responses, Previously, we described the expression and regulation in brain of an inducible form of prostaglandin synthase/cyclooxygenase, termed COX-2, COX-2 is a rate-limiting enzyme in prostanoid synthesis and its expression is rapidly regulated in developing and adult forebrain by physiological synaptic activity, Here we demonstrate that COX-2 immunoreactivity is selectively expressed in a subpopulation of excitatory neurons in neo- and allocortices, hippocampus, and amygdala and is compartmentalized to dendritic arborizations, Moreover, COX-2 immunoreactivity is present in dendritic spines, which are specialized structures involved in synaptic signaling, The developmental profile of COX-2 expression in dendrites follows well known histogenetic gradients and coincides with the critical period for activity-dependent synaptic remodeling, These results suggest that COX-2, and its diffusible prostanoid products, may play a role in postsynaptic signaling of excitatory neurons in cortex and associated structures.
    BibTeX:
    @article{Kaufmann1996,
      author = {Kaufmann, WE and Worley, PF and Pegg, J and Bremer, M and Isakson, P},
      title = {COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1996},
      volume = {93},
      number = {6},
      pages = {2317-2321}
    }
    
    Kaye, J., Swihart, T., Howieson, D., Dame, A., Moore, M., Karnos, T., Camicioli, R., Ball, M., Oken, B. & Sexton, G. Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia {1997} NEUROLOGY
    Vol. {48}({5}), pp. {1297-1304} 
    article  
    Abstract: Objective: To determine initial locus and rate of degeneration of temporal lobe structures (total lobe, hippocampus and parahippocampus) in preclinical dementia. Background: Postmortem studies suggest that the earliest changes in Alzheimer's disease are neurofibrillary tangle formation in hippocampus and adjacent cortex. MRI volume analysis of temporal lobe structures over time in subjects prior to developing dementia may allow the identification of when these processes begin, the rate they develop, and which areas are key to symptom development. Methods: 30 nondemented (NoD), healthy, elderly individuals enrolled in a prospective study of healthy aging evaluated annually over a mean of 42 months. Twelve subjects with subsequent cognitive decline were assigned to the preclinical dementia group (PreD). All 120 annual MRI studies analyzed by volumetric techniques assessed group differences in temporal lobe volumes and rates of brain loss. Results: NoD as well as PreD subjects had significant, time-dependent decreases in hippocampal and parahippocampal volume. Rates of volume loss between the groups did not significantly differ. PreD cases had significantly smaller hippocampi when asymptomatic. Parahippocampal volume did not differ between PreD and NoD cases. Significant time-dependent temporal lobe atrophy was present only in PreD. Conclusions: Hippocampal and parahippocampal atrophy occurs at a similar rate regardless of diagnostic group. Those who develop dementia may have smaller hippocampi to begin with, but become symptomatic because of accelerated loss of temporal lobe volume. Temporal lobe volume loss may mark the beginning of the disease process within six years prior to dementia onset.
    BibTeX:
    @article{Kaye1997,
      author = {Kaye, JA and Swihart, T and Howieson, D and Dame, A and Moore, MM and Karnos, T and Camicioli, R and Ball, M and Oken, B and Sexton, G},
      title = {Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia},
      journal = {NEUROLOGY},
      publisher = {LIPPINCOTT-RAVEN PUBL},
      year = {1997},
      volume = {48},
      number = {5},
      pages = {1297-1304}
    }
    
    Kelley, A. Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning {2004} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {27}({8}), pp. {765-776} 
    article DOI  
    Abstract: The nucleus accumbens is a brain region that participates in the control of behaviors related to natural reinforcers, such as ingestion, sexual behavior, incentive and instrumental learning, and that also plays a role in addictive processes. This paper comprises a review of work from our laboratory that focuses on two main research areas: (i) the role of the nucleus accumbens in food motivation, and (ii) its putative functions in cellular plasticity underlying appetitive learning. First, work within a number of different behavioral paradigms has shown that accumbens neurochemical systems play specific and dissociable roles in different aspects of food seeking and food intake, and part of this function depends on integration with the lateral hypothalamus and amygdala. We propose that the nucleus accumbens integrates information related to cognitive, sensory, and emotional processing with hypothalamic mechanisms mediating energy balance. This system as a whole enables complex hierarchical control of adaptive ingestive behavior. Regarding the second research area, our studies examining acquisition of lever-pressing for food in rats have shown that activation of glutamate N-methyl-D-aspartate (NMDA) receptors, within broadly distributed but interconnected regions (nucleus accumbens core, posterior striatum, prefrontal cortex, basolateral and central amygdala), is critical for such learning to occur. This receptor stimulation triggers intracellular cascades that involve protein phosphorylation and new protein synthesis. It is hypothesized that activity in this distributed network (including D1 receptor activity) computes coincident events and thus enhances the probability that temporally related actions and events (e.g. lever pressing and delivery of reward) become associated. Such basic mechanisms of plasticity within this reinforcement learning network also appear to be profoundly affected in addiction. (C) 2003 Elsevier Ltd. All rights reserved.
    BibTeX:
    @article{Kelley2004,
      author = {Kelley, AE},
      title = {Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2004},
      volume = {27},
      number = {8},
      pages = {765-776},
      note = {Symposium on Foundations and Innovations in the Neuroscience of Drug Abuse, BETHESDA, MARYLAND, MAY 14-15, 2003},
      doi = {{10.1016/j.neubiorev.2003.11.015}}
    }
    
    Kelley, A. & Berridge, K. The neuroscience of natural rewards: Relevance to addictive drugs {2002} JOURNAL OF NEUROSCIENCE
    Vol. {22}({9}), pp. {3306-3311} 
    article  
    BibTeX:
    @article{Kelley2002,
      author = {Kelley, AE and Berridge, KC},
      title = {The neuroscience of natural rewards: Relevance to addictive drugs},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2002},
      volume = {22},
      number = {9},
      pages = {3306-3311}
    }
    
    Keverne, E. The vomeronasal organ {1999} SCIENCE
    Vol. {286}({5440}), pp. {716-720} 
    article  
    Abstract: The vomeronasal organ (VNO) is a chemoreceptor organ enclosed in a cartilaginous capsule and separated from the main olfactory epithelium. The vomeronasal neurons have two distinct types of receptor that differ from each other and from the large family of odorant receptors, The VNO receptors are seven-transmembrane receptors coupled to CTP-binding protein, but appear to activate inositol 1,4,5-trisphosphate signaling as opposed to cyclic adenosine monophosphate. The nature of stimulus access suggests that the VNO responds to nonvolatile cues, leading to activation of the hypothalamus by way of the accessory olfactory bulb and amygdala. The areas of hypothalamus innervated regulate reproductive, defensive, and ingestive behavior as well as neuroendocrine secretion.
    BibTeX:
    @article{Keverne1999,
      author = {Keverne, EB},
      title = {The vomeronasal organ},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {1999},
      volume = {286},
      number = {5440},
      pages = {716-720}
    }
    
    KEVETTER, G. & WINANS, S. CONNECTIONS OF THE CORTICOMEDIAL AMYGDALA IN THE GOLDEN-HAMSTER .1. EFFERENTS OF THE VOMERONASAL-AMYGDALA {1981} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {197}({1}), pp. {81-98} 
    article  
    BibTeX:
    @article{KEVETTER1981,
      author = {KEVETTER, GA and WINANS, SS},
      title = {CONNECTIONS OF THE CORTICOMEDIAL AMYGDALA IN THE GOLDEN-HAMSTER .1. EFFERENTS OF THE VOMERONASAL-AMYGDALA},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1981},
      volume = {197},
      number = {1},
      pages = {81-98}
    }
    
    Killcross, S., Robbins, T. & Everitt, B. Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala {1997} NATURE
    Vol. {388}({6640}), pp. {377-380} 
    article  
    Abstract: The amygdala has long been thought to be involved in emotional behaviour(1,2), and its role in anxiety and conditioned fear has been highlighted(3,4). Individual amygdaloid nuclei have been shown to project to various cortical and subcortical regions implicated in affective processing(5-7). Here we show that some of these nuclei have separate roles in distinct mechanisms underlying conditioned fear responses. Rats with lesions of the central nucleus exhibited reduction in the suppression of behaviour elicited by a conditioned fear stimulus, but were simultaneously able to direct their actions to avoid further presentations of this aversive stimulus. In contrast, animals with lesions of the basolateral amygdala were unable to avoid the conditioned aversive stimulus by their choice behaviour, but exhibited normal conditioned suppression to this stimulus. This double dissociation demonstrates that distinct neural systems involving separate amygdaloid nuclei mediate different types of conditioned fear behaviour. We suggest that theories of amygdala function should take into account the roles of discrete amygdala subsystems in controlling different components of integrated emotional responses.
    BibTeX:
    @article{Killcross1997,
      author = {Killcross, S and Robbins, TW and Everitt, BJ},
      title = {Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1997},
      volume = {388},
      number = {6640},
      pages = {377-380}
    }
    
    KILLIANY, R., MOSS, M., ALBERT, M., SANDOR, T., TIEMAN, J. & JOLESZ, F. TEMPORAL-LOBE REGIONS ON MAGNETIC-RESONANCE-IMAGING IDENTIFY PATIENTS WITH EARLY ALZHEIMERS-DISEASE {1993} ARCHIVES OF NEUROLOGY
    Vol. {50}({9}), pp. {949-954} 
    article  
    Abstract: Objective.-The goal of the study was to examine the volume of selected brain regions in a group of mildly impaired patients with Alzheimer's disease (AD). Five regions were selected for analysis, all of which have been reported to show substantial change in the majority of patients with AD at some time in the course of disease. Design.-Case-control study with the experimenter `'blinded.'' Setting.-Hospital-based magnetic resonance imaging center. Participants.-Fifteen subjects, eight patients with the diagnosis of probable dementia of the Alzheimer type made in concordance with National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria and seven age-matched healthy control subjects. Results.-Three of the volumetric measures were significantly different between patients with AD and controls: the hippocampus, the temporal horn of the lateral ventricles, and the temporal lobe. Two of the measures did not significantly differentiate patients with AD and controls: the amygdala and the basal forebrain. A discriminant function analysis demonstrated that a linear combination of the volumes of the hippocampus and the temporal horn of the lateral ventricles differentiated 100% of the patients and controls from one another. Conclusions.-The results suggest that the hippocampus and the temporal horn of the lateral ventricles may be useful as antemortem markers of AD in mildly impaired patients.
    BibTeX:
    @article{KILLIANY1993,
      author = {KILLIANY, RJ and MOSS, MB and ALBERT, MS and SANDOR, T and TIEMAN, J and JOLESZ, F},
      title = {TEMPORAL-LOBE REGIONS ON MAGNETIC-RESONANCE-IMAGING IDENTIFY PATIENTS WITH EARLY ALZHEIMERS-DISEASE},
      journal = {ARCHIVES OF NEUROLOGY},
      publisher = {AMER MEDICAL ASSOC},
      year = {1993},
      volume = {50},
      number = {9},
      pages = {949-954}
    }
    
    KIM, J., RISON, R. & FANSELOW, M. EFFECTS OF AMYGDALA, HIPPOCAMPUS, AND PERIAQUEDUCTAL GRAY LESIONS ON SHORT-TERM AND LONG-TERM CONTEXTUAL FEAR {1993} BEHAVIORAL NEUROSCIENCE
    Vol. {107}({6}), pp. {1093-1098} 
    article  
    Abstract: The effects of amygdala, hippocampus, and periaqueductal gray (PAG) lesions on contextual fear conditioning in rats were examined. Freezing behavior served as the measure of conditioning. Unlesioned control animals showed reliable conditional freezing in the testing chamber when observed both immediately and 24 hr after footshocks. In contrast, rats with amygdala or ventral PAG lesions exhibited a significant attenuation in freezing both immediately and 24 hr after the shocks. Dorsal PAG lesions had no effect on freezing at either time. Animals with hippocampal lesions displayed robust freezing behavior immediately following the shock, even though they showed a marked deficit in freezing 24 hr after the shock. These results indicate that there are anatomically dissociable short- and long-term conditional fear states.
    BibTeX:
    @article{KIM1993,
      author = {KIM, JJ and RISON, RA and FANSELOW, MS},
      title = {EFFECTS OF AMYGDALA, HIPPOCAMPUS, AND PERIAQUEDUCTAL GRAY LESIONS ON SHORT-TERM AND LONG-TERM CONTEXTUAL FEAR},
      journal = {BEHAVIORAL NEUROSCIENCE},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1993},
      volume = {107},
      number = {6},
      pages = {1093-1098}
    }
    
    Klitgaard, H., Matagne, A., Gobert, J. & Wulfert, E. Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy {1998} EUROPEAN JOURNAL OF PHARMACOLOGY
    Vol. {353}({2-3}), pp. {191-206} 
    article  
    Abstract: The protective and adverse effect potentials of levetiracetam ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide) in rodent models of seizures and epilepsy were compared with the profile of several currently prescribed and newly developed antiepileptic drugs. Levetiracetam was devoid of anticonvulsant activity in the acute maximal electroshock seizure test and in the maximal pentylenetetrazol seizure test in mice (up to 540 mg/kg, i.p.) but exhibited potent protection against generalised epileptic seizures in electrically and pentylenetetrazol-kindled mice (ED50 values = 7 and 36 mg/kg, respectively, i.p.). This differs markedly from established and most new antiepileptic drugs which induce significant protection in both the acute seizure tests and the kindling models. Furthermore, levetiracetam was devoid of anticonvulsant activity in several maximal chemoconvulsive seizure tests although an interesting exception was the potent protection observed against secondarily generalised activity from focal seizures induced by pilocarpine in mice (ED50 value = 7 mg/kg, i.p.), pilocarpine and kainic acid in rats (minimum active dose = 17 and 54 mg/kg, respectively, i.p.). The protection afforded by levetiracetam on the threshold for methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM)-induced seizures persisted after chronic administration (17-170 mg/kg, i.p., twice daily/14 days) and levetiracetam did not lower the seizure threshold for the proconvulsant action of the inverse benzodiazepine receptor agonist, N-methyl-beta-carboline-3-carboxamide (FG 7142). The main metabolite of levetiracetam (ucb L057; (S)-alpha-ethyl-2-oxo-1-pyrrolidine acetic acid) was found to be inactive in sound-sensitive mice after acute administration of doses up to 548 mg/kg, i.p. Levetiracetam induced only minor behavioural alterations in both normal and amygdala-kindled rats (54-1700 mg/kg, i.p.) resulting in an unusually high safety margin between rotarod impairment and seizure suppression of 148 in corneally kindled mice and 235 in Genetic Absence Epilepsy Rats from Strasbourg. In comparison, existing antiepileptic drugs have ratios between 2 and 17 in the corneally kindled mouse model. These studies reveal a unique profile of levetiracetam in rodent models. Characteristics are a general lack of anticonvulsant activity against maximal, acute seizures and selective protection with a very high safety margin in genetic and kindled animals and against chemoconvulsants producing partial epileptic seizures. This activity differs markedly from that of the established and newly introduced antiepileptic drugs and appears to derive from the parent compound since its major metabolite was inactive in all models studied. Together these results therefore suggest that levetiracetam may offer an effective, broad-spectrum treatment of epileptic seizures in patients, with a minimum of adverse effects. (C) 1998 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Klitgaard1998,
      author = {Klitgaard, H and Matagne, A and Gobert, J and Wulfert, E},
      title = {Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy},
      journal = {EUROPEAN JOURNAL OF PHARMACOLOGY},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1998},
      volume = {353},
      number = {2-3},
      pages = {191-206}
    }
    
    de Kloet, E., Oitzl, M. & Joels, M. Stress and cognition: are corticosteroids good or bad guys? {1999} TRENDS IN NEUROSCIENCES
    Vol. {22}({10}), pp. {422-426} 
    article  
    Abstract: Corticosteroid hormones secreted by the adrenal cortex protect the brain against: adverse events and are essential for cognitive performance. However, in recent literature, the central action of corticosteroids has mostly been portrayed as damaging and disruptive to memory formation. We argue that this paradox can be explained by appreciating the specific role of both mineralocorticoid and glucocorticoid receptors in the various stages of information processing. In addition,the context in which corticosteroid-receptor activation takes place is crucial in determining steroid-mediated effects. These effects generally favour adaptive behaviour that is most relevant to the situation. Corticosteroid effects on cognition can, however,turn from adaptive into maladaptive,when actions via the two corticosteroid-receptor types are imbalanced for a prolonged period of time.
    BibTeX:
    @article{Kloet1999,
      author = {de Kloet, ER and Oitzl, MS and Joels, M},
      title = {Stress and cognition: are corticosteroids good or bad guys?},
      journal = {TRENDS IN NEUROSCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {1999},
      volume = {22},
      number = {10},
      pages = {422-426}
    }
    
    Koh, J., Suh, S., Gwag, B., He, Y., Hsu, C. & Choi, D. The role of zinc in selective neuronal death after transient global cerebral ischemia {1996} SCIENCE
    Vol. {272}({5264}), pp. {1013-1016} 
    article  
    Abstract: Zinc is present in presynaptic nerve terminals throughout the mammalian central nervous system and likely serves as an endogenous signaling substance. However, excessive exposure to extracellular zinc can damage central neurons. After transient forebrain ischemia in rats, chelatable zinc accumulated specifically in degenerating neurons in the hippocampal hilus and CA1, as well as in the cerebral cortex, thalamus, striatum, and amygdala. This accumulation preceded neurodegeneration, which could be prevented by the intraventricular injection of a zinc chelating agent. The toxic influx of zinc may be a key mechanism underlying selective neuronal death after transient global ischemic insults.
    BibTeX:
    @article{Koh1996,
      author = {Koh, JY and Suh, SW and Gwag, BJ and He, YY and Hsu, CY and Choi, DW},
      title = {The role of zinc in selective neuronal death after transient global cerebral ischemia},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {1996},
      volume = {272},
      number = {5264},
      pages = {1013-1016}
    }
    
    Konig, M., Zimmer, A., Steiner, H., Holmes, P., Crawley, J., Brownstein, M. & Zimmer, A. Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin {1996} NATURE
    Vol. {383}({6600}), pp. {535-538} 
    article  
    Abstract: ENKEPHALINS are endogenous opioid peptides that are derived from a pre-proenkephalin precursor protein(1,2). They are thought to be vital in regulating many physiological functions, including pain perception and analgesia, responses to stress, aggression and dominance (3-5). Here we have used a genetic approach to study the role of the mammalian opioid system. We disrupted the preproenkephalin gene using homologous recombination in embryonic stem cells to generate enkephalin-deficient mice. Mutant enk(-/-) animals are healthy, fertile, and care for their offspring, but display significant behavioural abnormalities. Mice with the enk(-/-) genotype are more anxious and males display increased offensive aggressiveness. Mutant animals show marked differences from controls in supraspinal, but not in spinal, responses to painful stimuli. Unexpectedly, enk(-/-) mice exhibit normal stress-induced analgesia. Our results show that enkephalins modulate responses to painful stimuli. Thus, genetic factors may contribute significantly to the experience of pain.
    BibTeX:
    @article{Konig1996,
      author = {Konig, M and Zimmer, AM and Steiner, H and Holmes, PV and Crawley, JN and Brownstein, MJ and Zimmer, A},
      title = {Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1996},
      volume = {383},
      number = {6600},
      pages = {535-538}
    }
    
    Koob, G. Alcoholism: Allostasis and beyond {2003} ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
    Vol. {27}({2}), pp. {232-243} 
    article DOI  
    Abstract: Alcoholism is a chronic relapsing disorder characterized by compulsive drinking, loss of control over intake, and impaired social and occupational function. Animal models have been developed for various stages of the alcohol addiction cycle with a focus on the motivational effects of withdrawal, craving, and protracted abstinence. A conceptual framework focused on allostatic changes in reward function that lead to excessive drinking provides a heuristic framework with which to identify the neurobiologic mechanisms involved in the development of alcoholism. Neuropharmacologic studies in animal models have provided evidence for specific neurochemical mechanisms in specific brain reward and stress circuits that become dysregulated during the development of alcohol dependence. The brain reward system implicated in the development of alcoholism comprises key elements of a basal forebrain macrostructure termed the,extended amygdala that includes the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and a transition zone in the medial (shell) part of the nucleus accumbens. There are multiple neurotransmitter systems that converge on the extended amygdala that become dysregulated during the development of alcohol dependence, including gamma-aminobutyric acid, opioid peptides, glutamate, serotonin, and dopamine. In addition, the brain stress systems may contribute significantly to the allostatic state. During the development of alcohol dependence, corticotropin-releasing factor may be recruited, and the neuropeptide Y brain antistress system may be compromised. These changes in the reward and stress systems are hypothesized to maintain hedonic stability in an allostatic state, as opposed to a homeostatic state, and as such convey the vulnerability for relapse in recovering alcoholics. The allostatic model not only integrates molecular, cellular, and circuitry neuroadaptations in brain motivational systems produced by chronic alcohol ingestion with genetic vulnerability but also provides a key to translate advances in animal studies to the human condition.
    BibTeX:
    @article{Koob2003,
      author = {Koob, GF},
      title = {Alcoholism: Allostasis and beyond},
      journal = {ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH},
      publisher = {LIPPINCOTT WILLIAMS & WILKINS},
      year = {2003},
      volume = {27},
      number = {2},
      pages = {232-243},
      doi = {{10.1097/01.ALC.0000057122.36127.C2}}
    }
    
    Koob, G. Corticotropin-releasing factor, norepinephrine, and stress {1999} BIOLOGICAL PSYCHIATRY
    Vol. {46}({9}), pp. {1167-1180} 
    article  
    Abstract: Corticotropin-releasing factor (CRF) and related peptides in the central nervous system appears to have activating properties on behavior and to enhance behavioral responses to stressors. CRF and urocortin injected into the brain produces increases in arousal as measured by locomotor activation and increased responsiveness to stressful stimuli. These effects of CRF appear to be independent of the pituitary adrenal axis and can be reversed by specific and selective CRF antagonists alpha-helical CRF9-41 and D-Phe CRF12-41. Perhaps more importantly, CRF antagonists can reverse behavioral responses to many stressors. These results suggest that endogenous CRF systems in the brain may have a role in mediating behavioral responses to stressors. Norepinephrine systems emanating from the nucleus locus coeruleus also long have been hypothesized to be involved in mediating behavioral constructs associated with alertness, arousal, and stress. Pharmacologic, physiologic, and neuroanatomic evidence supports an important role for a CRF-norepinephrine interaction in the region of the locus coeruleus in response to stressors that may be modality-specific where CRF neurons activate the locus coeruleus. One may hypothesize that another norepinephrine-CRF interaction may occur in the terminal projections of the forebrain norepinephrine systems in the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala where norepinephrine stimulates CRF release, Such a feed-forward system may be particularly important in situations where an organism must mobilize not only the pituitary adrenal system but also the central nervous system, in response to environmental challenge. However such a feed-forward mechanism in a fundamental brain-activating system may be particularly vulnerable to dysfunction and thus, may be the key to a variety of patho-physiologic conditions involving abnormal responses to stressors such as anorexia nervosa, anxiety, and affective disorders. (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Koob1999a,
      author = {Koob, GF},
      title = {Corticotropin-releasing factor, norepinephrine, and stress},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1999},
      volume = {46},
      number = {9},
      pages = {1167-1180},
      note = {Conference on Norepinephrine - New Vistas for and Old Neurotransmitter, KEY WEST, FLORIDA, MAR, 1999}
    }
    
    Koob, G. & Heinrichs, S. A role for corticotropin releasing factor and urocortin in behavioral responses to stressors {1999} BRAIN RESEARCH
    Vol. {848}({1-2}), pp. {141-152} 
    article  
    Abstract: Corticotropin-releasing factor (CRF) and CRF-related neuropeptides have an important role in the central nervous system to mediate behavioral responses to stressors, CRF receptor antagonists are very effective in reversing stress-induced suppression and activation in behavior. An additional CRF-like neuropeptide, urocortin, has been identified in the brain and has a high affinity for the CRF-2 receptor in addition to the CRF-1 receptor. Urocortin has many of the effects of CRF but also is significantly more potent than CRF in decreasing feeding in both meal-deprived and free-feeding rats. In mouse genetic models, mice over-expressing CRF show anxiogenic-like responses compared to wild-type mice, and mice lacking the CRF-1 receptor showed an anxiolytic-like behavioral profile compared to wild-type mice. Results to date have led to the hypothesis that CRF-1 receptors may mediate CRF-like neuropeptide effects on behavioral responses to stressors, but CRF-2 receptors may mediate the suppression of feeding produced by CRF-Like neuropeptides. Brain sites for the behavioral effects of CRF include the locus coeruleus (LC), paraventricular nucleus (PVN) of the hypothalamus, the bed nucleus of the stria terminalis (BNST), and the central nucleus of the amygdala. CRF may also be activated during acute withdrawal from all major drugs of abuse, and recent data suggest that CRF may contribute to the dependence and vulnerability to relapse associated with chronic administration of drugs of abuse. These data suggest that CRF systems in the brain have a unique role in mediating behavioral responses to diverse stressors. These systems may be particularly important in situations were an organism must mobilize not only the pituitary adrenal system, but also the central nervous system in response to environmental challenge. Clearly, dysfunction in such a fundamental brain-activating system may be the key to a variety of pathophysiological conditions involving abnormal responses to stressors such as anxiety disorders, affective disorders, and anorexia nervosa. (C) 1999 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Koob1999,
      author = {Koob, GF and Heinrichs, SC},
      title = {A role for corticotropin releasing factor and urocortin in behavioral responses to stressors},
      journal = {BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1999},
      volume = {848},
      number = {1-2},
      pages = {141-152},
      note = {2nd Brain Research interactive Symposium, MIAMI, FLORIDA, OCT 21-23, 1999}
    }
    
    Koob, G. & Nestler, E. The neurobiology of drug addiction {1997} JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
    Vol. {9}({3}), pp. {482-497} 
    article  
    Abstract: Animal models have begun to provide insights into the neurobiological basis of reinforcement in drug addiction. The reinforcing effects of indirect sympathomimetics such as cocaine and amphetamine appear to depend on release of dopamine in the terminal fields of the mesocorticolimbic dopamine system. The acute reinforcing effects of opiates involve not only an activation of dopamine, but also dopamine-independent elements in the terminal regions of the mesocorticolimbic dopamine system. Nicotine's reinforcing effects may involve both dopaminergic and opioid peptidergic systems. Ethanol's reinforcing effects may result from multiple neurotransmitter interactions including gamma-aminobutyric acid, glutamate, dopamine, opioid peptides, and serotonin. Subtle changes in neurochemical function and signal transduction and transcription mechanisms in sensitive neuronal elements in the extended amygdala may be mediators of chronic drug action that lead to vulnerability to relapse and may provide exciting insight into the neuroadaptations associated with drug addiction.
    BibTeX:
    @article{Koob1997,
      author = {Koob, GF and Nestler, EJ},
      title = {The neurobiology of drug addiction},
      journal = {JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES},
      publisher = {AMER PSYCHIATRIC ASSOCIATION},
      year = {1997},
      volume = {9},
      number = {3},
      pages = {482-497}
    }
    
    Koob, G., Roberts, A., Schulteis, G., Parsons, L., Heyser, C., Hyytia, P., Merlo-Pich, E. & Weiss, F. Neurocircuitry targets in ethanol reward and dependence {1998} ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
    Vol. {22}({1}), pp. {3-9} 
    article  
    Abstract: Alcoholism is a complex behavioral disorder characterized by excessive consumption of ethanol, a narrowing of the behavioral repertoire toward excessive consumption, the development of tolerance and dependence, and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome. Recent work has begun to define the neurocircuits responsible for the two major sources of reinforcement key to animal models of excessive ethanol intake: positive and negative reinforcement. Ethanol appears to interact with ethanol-sensitive elements within neuronal membranes that convey the specificity of neurochemical action. Ethanol reinforcement appears to be mediated by an activation of GABA-A receptors, release of opioid peptides, release of dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic ethanol administration as reflected by opposite effects during acute ethanol withdrawal and by the recruitment of other neurotransmitter systems such as the stress neuropeptide corticotropin-releasing factor. Future challenges will include a focus on understanding how these neuroadaptive changes convey vulnerability to relapse in animals with a history of ethanol dependence.
    BibTeX:
    @article{Koob1998,
      author = {Koob, GF and Roberts, AJ and Schulteis, G and Parsons, LH and Heyser, CJ and Hyytia, P and Merlo-Pich, E and Weiss, F},
      title = {Neurocircuitry targets in ethanol reward and dependence},
      journal = {ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH},
      publisher = {LIPPINCOTT WILLIAMS & WILKINS},
      year = {1998},
      volume = {22},
      number = {1},
      pages = {3-9},
      note = {Symposium on Approaches for Studying Neural Circuits - Application to Alcohol Research at the 26th Annual Meeting of the Society-for-Neuroscience, WASHINGTON, D.C., NOV 16, 1996}
    }
    
    Koylu, E., Couceyro, P., Lambert, P. & Kuhar, M. Cocaine- and amphetamine-regulated transcript peptide immunohistochemical localization in the rat brain {1998} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {391}({1}), pp. {115-132} 
    article  
    Abstract: Cocaine- and amphetamine-regulated transcript (CART) is a brain-enriched mRNA with a protein product(s) that is a candidate brain neurotransmitter. We have developed antisera to CART peptide fragment 106-129 and have demonstrated specific immunoreactivity (IR) at the light microscopic level throughout the brain, spinal cord, and retina. All brain nuclei previously shown to express CART mRNA are now shown to contain CART peptide IR. Although it is premature to define CART peptide(s) as a neurotransmitter(s), the localization found here suggests an involvement of CART in many processes. CART peptide staining in the nucleus accumbens and basolateral amygdala continue to suggest a role in drug-induced reward and reinforcement. Staining in the olfactory bulbs, the cortical barrels, the retina and its projection areas, the thalamic nuclei, the lateral and dorsal horns of the spinal cord, and the nuclei of the solitary tract are compatible with a major role for CART in sensory processing and autonomic regulation. CART peptides appear to colocalize with some classical neurotransmitters and appear to occur in peripheral neurons as well. (C) 1998 Wiley-Liss, Inc.
    BibTeX:
    @article{Koylu1998,
      author = {Koylu, EO and Couceyro, PR and Lambert, PD and Kuhar, MJ},
      title = {Cocaine- and amphetamine-regulated transcript peptide immunohistochemical localization in the rat brain},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1998},
      volume = {391},
      number = {1},
      pages = {115-132}
    }
    
    Kringelbach, M. & Rolls, E. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology {2004} PROGRESS IN NEUROBIOLOGY
    Vol. {72}({5}), pp. {341-372} 
    article DOI  
    Abstract: The human orbitofrontal cortex is an important brain region for the processing of rewards and punishments, which is a prerequisite for the complex and flexible emotional and social behaviour which contributes to the evolutionary success of humans. Yet much remains to be discovered about the functions of this key brain region, and new evidence from functional neuroimaging and clinical neuropsychology is affording new insights into the different functions of the human orbitofrontal cortex. We review the neuroanatomical and neuropsychological literature on the human orbitofrontal cortex, and propose two distinct trends of neural activity based on a meta-analysis of neuroimaging studies. One is a mediolateral distinction, whereby medial orbitofrontal cortex activity is related to monitoring the reward value of many different reinforcers, whereas lateral orbitofrontal cortex activity is related to the evaluation of punishers which may lead to a change in ongoing behaviour. The second is a posterior-anterior distinction with more complex or abstract reinforcers (such as monetary gain and loss) represented more anteriorly in the orbitofrontal cortex than simpler reinforcers such as taste or pain. Finally, we propose new neuroimaging methods for obtaining further evidence on the localisation of function in the human orbitofrontal cortex. (C) 2004 Elsevier Ltd. All rights reserved.
    BibTeX:
    @article{Kringelbach2004,
      author = {Kringelbach, ML and Rolls, ET},
      title = {The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology},
      journal = {PROGRESS IN NEUROBIOLOGY},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2004},
      volume = {72},
      number = {5},
      pages = {341-372},
      doi = {{10.1016/j.pneurobio.2004.03.006}}
    }
    
    LaBar, K., Gatenby, J., Gore, J., LeDoux, J. & Phelps, E. Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study {1998} NEURON
    Vol. {20}({5}), pp. {937-945} 
    article  
    Abstract: Echoplanar functional magnetic resonance imaging (fMRI) was used in normal human subjects to investigate the role of the amygdala in conditioned fear acquisition and extinction. A simple discrimination procedure was employed in which activation to a visual cue predicting shock (CS+) was compared with activation to another cue presented alone (CS-). CS+ and CS-trial types were intermixed in a pseudorandom order. Functional images were acquired with an asymmetric spin echo pulse sequence from three coronal slices centered on the amygdala. Activation of the amygdala/periamygdaloid cortex was observed during conditioned fear acquisition and extinction. The extent of activation during acquisition was significantly correlated with autonomic indices of conditioning in individual subjects. Consistent with a recent electrophysiological recording study in the rat (Quirk et at., 1997), the profile of the amygdala response was temporally graded, although this dynamic was only statistically reliable during extinction. These results provide further evidence for the conservation of amygdala function across species and implicate an amygdalar contribution to both acquisition and extinction processes during associative emotional learning tasks.
    BibTeX:
    @article{LaBar1998,
      author = {LaBar, KS and Gatenby, JC and Gore, JC and LeDoux, JE and Phelps, EA},
      title = {Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {1998},
      volume = {20},
      number = {5},
      pages = {937-945}
    }
    
    LABAR, K., LEDOUX, J., SPENCER, D. & PHELPS, E. IMPAIRED FEAR CONDITIONING FOLLOWING UNILATERAL TEMPORAL LOBECTOMY IN HUMANS {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({10}), pp. {6846-6855} 
    article  
    Abstract: Classical fear conditioning was used in the present study as a model for investigating emotional learning and memory in human subjects with lesions to the medial temporal lobe. Animal studies have revealed a critical role for medial temporal lobe structures, particularly the amygdala, in simple and complex associative emotional responding. Whether these structures perform similar functions in humans is unknown. On both simple and conditional discrimination tasks, unilateral temporal lobectomy subjects showed impaired conditioned response acquisition relative to control subjects. This impairment could not be accounted for by deficits in nonassociative sensory or autonomic performance factors, or by differences in declarative memory for the experimental parameters. These results show that medial temporal lobe structures in humans, as in other mammals, are important components in an emotional memory network.
    BibTeX:
    @article{LABAR1995,
      author = {LABAR, KS and LEDOUX, JE and SPENCER, DD and PHELPS, EA},
      title = {IMPAIRED FEAR CONDITIONING FOLLOWING UNILATERAL TEMPORAL LOBECTOMY IN HUMANS},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1995},
      volume = {15},
      number = {10},
      pages = {6846-6855}
    }
    
    Ladd, C., Owens, M. & Nemeroff, C. Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation {1996} ENDOCRINOLOGY
    Vol. {137}({4}), pp. {1212-1218} 
    article  
    Abstract: There is considerable evidence that CRF-containing neurons integrate the endocrine, autonomic, immune, and behavioral responses to stress. In this study we examined long term effects of early stress on developing hypothalamic and extrahypothalamic CBF neural systems in the rat brain and subsequent responses to stress in the adult. Specifically, we sought to determine whether adult male rats previously isolated for 6 h daily during postnatal days 2-20 react in a biochemically distinct manner to a mild foot shock stress compared to controls. Four treatment groups were examined: nondeprived (NDEP)/no shock, NDEP/shock, deprived (DEP)/no shock, and DEP/shock. Compared to the NDEP group, DEP rats exhibited an increase in both basal and stress-induced ACTH concentrations. Moreover, DEP rats exhibited a 125% increase in immunoreactive CRF concentrations in the median eminence and a reduction in the density of CRF receptor binding in the anterior pituitary compared to those in all NDEP rats. Alterations in extrahypothalamic CRF systems were also apparent in DEP vs. NDEP animals, with an observed 59% increase in the number of CRF receptor-binding sites in the raphe nucleus and an 86% increase in immunoreactive CRF concentrations in the parabrachial nucleus. These results indicate that maternal deprivation before weaning in male rats produces effects on CRF neural systems in both the central nervous system and pituitary that are apparent several months later and are probably associated with persistent alterations in behavioral responses in adult rats.
    BibTeX:
    @article{Ladd1996,
      author = {Ladd, CO and Owens, MJ and Nemeroff, CB},
      title = {Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation},
      journal = {ENDOCRINOLOGY},
      publisher = {ENDOCRINE SOC},
      year = {1996},
      volume = {137},
      number = {4},
      pages = {1212-1218}
    }
    
    Lane, R., Reiman, E., Axelrod, B., Yun, L., Holmes, A. & Schwartz, G. Neural correlates of levels of emotional awareness: Evidence of an interaction between emotion and attention in the anterior cingulate cortex {1998} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {10}({4}), pp. {525-535} 
    article  
    Abstract: Recent functional imaging studies have begun to identify the neural correlates of emotion in healthy volunteers. However, studies to date have not differentially addressed the brain areas associated with the perception, experience, or expression of emotion during emotional arousal. To explore the neural correlates of emotional experience, we used positron emission tomography (PET) and O-15-water to measure cerebral blood flow (CBF) in 12 healthy women during film and recall-induced emotion and correlated CBF changes attributable to emotion with subjects' scores on the Levels of Emotional Awareness Scale (LEAS), a measure of individual differences in the capacity to experience emotion in a differentiated and complex way. A conjunction analysis revealed that the correlations between LEAS and CBF during film and recall-induced emotion overlapped significantly (z = 3.74, p < 0.001) in Brodmann's area 24 of the anterior cingulate cortex (ACC). This finding suggests that individual differences in the ability to accurately detect emotional signals interoceptively or exteroceptively may at least in part be a function of the degree to which the ACC participates in the experiential processing and response to emotion cues. To the extent that this finding is consistent with the functions of the ACC involving attention and response selection, it suggests that this neural correlate of conscious emotional experience is not exclusive to emotion.
    BibTeX:
    @article{Lane1998,
      author = {Lane, RD and Reiman, EM and Axelrod, B and Yun, LS and Holmes, A and Schwartz, GE},
      title = {Neural correlates of levels of emotional awareness: Evidence of an interaction between emotion and attention in the anterior cingulate cortex},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      publisher = {M I T PRESS},
      year = {1998},
      volume = {10},
      number = {4},
      pages = {525-535}
    }
    
    Lane, R., Reiman, E., Bradley, M., Lang, P., Ahern, G., Davidson, R. & Schwartz, G. Neuroanatomical correlates of pleasant and unpleasant emotion {1997} NEUROPSYCHOLOGIA
    Vol. {35}({11}), pp. {1437-1444} 
    article  
    Abstract: Substantial evidence suggests that a key distinction in the classification of human emotion is that between an appetitive motivational system associated with positive or pleasant emotion and an aversive motivational system associated with negative or unpleasant emotion. To explore the neural substrates of these two systems, 12 healthy women viewed sets of pictures previously demonstrated to elicit pleasant, unpleasant and neutral emotion, while positron emission tomographic (PET) measurements of regional cerebral blood flow were obtained. Pleasant and unpleasant emotions were each distinguished from neutral emotion conditions by significantly increased cerebral blood flow in the vicinity of the medial prefrontal cortex (Brodmann's area 9), thalamus, hypothalamus and midbrain (P < 0.005). Unpleasant was distinguished from neutral or pleasant emotion by activation of the bilateral occipito temporal cortex and cerebellum, and left parahippocampal gyrus, hippocampus and amygdala (P < 0.005). Pleasant was also distinguished from neutral but not unpleasant emotion by activation of the head of the left caudate nucleus (P < 0.005). These findings are consistent with those from other recent PET studies of human emotion and demonstrate that there are both common and unique components of the neural networks mediating pleasant and unpleasant emotion in healthy women. (C) 1997 Elsevier Science Ltd.
    BibTeX:
    @article{Lane1997,
      author = {Lane, RD and Reiman, EM and Bradley, MM and Lang, PJ and Ahern, GL and Davidson, RJ and Schwartz, GE},
      title = {Neuroanatomical correlates of pleasant and unpleasant emotion},
      journal = {NEUROPSYCHOLOGIA},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1997},
      volume = {35},
      number = {11},
      pages = {1437-1444}
    }
    
    Lang, P., Bradley, M. & Cuthbert, B. Emotion, motivation, and anxiety: Brain mechanisms and psychophysiology {1998} BIOLOGICAL PSYCHIATRY
    Vol. {44}({12}), pp. {1248-1263} 
    article  
    Abstract: The organization of response systems in emotion is founded on two basic motive systems, appetitive and defensive. The subcortical and deep cortical structures that determine primary motivated behavior are similar across mammalian species. Animal research has illuminated these neural systems and defined their reflex outputs. Although motivated behavior is more complex and varied in humans, the simpler underlying response patterns persist in affective expression. These basic phenomena are elucidated here in the context of affective perception. Thus, the research examines human beings watching uniquely human stimuli-primarily picture media (but also words and sounds) that prompt emotional arousal-showing how the underlying motivational structure is apparent in the organization of visceral and behavioral responses, in the priming of simple reflexes, and in the reentrant processing of these symbolic representations in the sensory cortex. Implications of the work for understanding pathological emotional states are discussed, emphasizing research on psychopathy and the anxiety disorders. Biol Psychiatry 1998;44:1248-1263 (C) 1998 Society of Biological Psychiatry.
    BibTeX:
    @article{Lang1998,
      author = {Lang, PJ and Bradley, MM and Cuthbert, BN},
      title = {Emotion, motivation, and anxiety: Brain mechanisms and psychophysiology},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1998},
      volume = {44},
      number = {12},
      pages = {1248-1263},
      note = {Research Symposium on Brain Neurocircuitry of Anxiety and Fear - Implications for Clinical Research and Practice, BOSTON, MASSACHUSETTS, MAR 26, 1998}
    }
    
    Lang, P., Davis, M. & Ohman, A. Fear and anxiety: animal models and human cognitive psychophysiology {2000} JOURNAL OF AFFECTIVE DISORDERS
    Vol. {61}({3}), pp. {137-159} 
    article  
    Abstract: The aim of this paper is to explicate what is special about emotional information processing, emphasizing the neural foundations that underlie the experience and expression of fear. A functional, anatomical model of defense behavior in animals is presented and applications are described in cognitive and physiological studies of human affect. It is proposed that unpleasant emotions depend on the activation of an evolutionarily primitive subcortical circuit, including the amygdala and the neural structures to which it projects. This motivational system mediates specific autonomic (e.g., heart rate change) and somatic reflexes (e.g., startle change) that originally promoted survival in dangerous conditions. These same response patterns are illustrated in humans, as they process objective, memorial, and media stimuli. Furthermore, it is shown how variations in the neural circuit and its outputs may separately characterize cue-specific fear las in specific phobia) and more generalized anxiety. Finally, again emphasizing links between the animal and human data, we focus on special, attentional features of emotional processing: The automaticity of fear reactions, hyper-reactivity to minimal threat-cues, and evidence that the physiological responses in fear may be independent of slower, language-based appraisal processes. (C) 2000 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Lang2000,
      author = {Lang, PJ and Davis, M and Ohman, A},
      title = {Fear and anxiety: animal models and human cognitive psychophysiology},
      journal = {JOURNAL OF AFFECTIVE DISORDERS},
      publisher = {ELSEVIER SCIENCE BV},
      year = {2000},
      volume = {61},
      number = {3},
      pages = {137-159}
    }
    
    Lawrie, S. & Abukmeil, S. Brain abnormality in schizophrenia - A systematic and quantitative review of volumetric magnetic resonance imaging studies {1998} BRITISH JOURNAL OF PSYCHIATRY
    Vol. {172}, pp. {110-120} 
    article  
    Abstract: Background Numerous in vivo brain imaging studies suggest that cerebral structure is abnormal in schizophrenia, but implicate different regions to varying extents. Method We identified published MRI studies in schizophrenia with searches of the computerised literature and key journals. Reports giving the volumes of cortical structures in people with schizophrenia and controls were included. The percentage differences in volumes were calculated and the median taken as a summary measure for each brain region. Results Forty relevant studies were identified. The median percentage volume differences revealed overall reductions in the whole brain (3, temporal robe (6% left, 9.5% right), and the amygdala/hippocampal complex (6.5 5.5; and increases in the lateral ventricles (44 36, that were greatest in the body and occipital horns. Segmentation studies suggest that grey matter is reduced but that white matter volumes may actually be increased. In men, substantial reductions were also evident in the amygdala and hippocampus, as well as the largest reductions of all in the parahippocampus (14 9. Few studies gave figures for women alone. Conclusions Several brain structures in schizophrenia are affected to a greater extent than expected from overall reductions in brain volume. Further studies are required in affected women, and to try to identify clinical and aetiological associations of these findings.
    BibTeX:
    @article{Lawrie1998,
      author = {Lawrie, SM and Abukmeil, SS},
      title = {Brain abnormality in schizophrenia - A systematic and quantitative review of volumetric magnetic resonance imaging studies},
      journal = {BRITISH JOURNAL OF PSYCHIATRY},
      publisher = {ROYAL COLLEGE OF PSYCHIATRISTS},
      year = {1998},
      volume = {172},
      pages = {110-120}
    }
    
    LeDoux, J. The emotional brain, fear, and the amygdala {2003} CELLULAR AND MOLECULAR NEUROBIOLOGY
    Vol. {23}({4-5}), pp. {727-738} 
    article  
    Abstract: 1. Considerable progress has been made over the past 20 years in relating specific circuits of the brain to emotional functions. Much of this work has involved studies of Pavlovian or classical fear conditioning, a behavioral procedure that is used to couple meaningless environmental stimuli to emotional (defense) response networks. 2. The major conclusion from studies of fear conditioning is that the amygdala plays critical role in linking external stimuli to defense responses. 3. Before describing research on the role of the amygdala in fear conditioning, though, it will be helpful to briefly examine the historical events that preceded modern research on conditioned fear.
    BibTeX:
    @article{LeDoux2003,
      author = {LeDoux, J},
      title = {The emotional brain, fear, and the amygdala},
      journal = {CELLULAR AND MOLECULAR NEUROBIOLOGY},
      publisher = {KLUWER ACADEMIC/PLENUM PUBL},
      year = {2003},
      volume = {23},
      number = {4-5},
      pages = {727-738}
    }
    
    LeDoux, J. Emotion circuits in the brain {2000} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {23}, pp. {155-184} 
    article  
    Abstract: The field of neuroscience has, after a long period of looking the other way, again embraced emotion as an important research area. Much of the progress has come from studies of fear, and especially fear conditioning. This work has pinpointed the amygdala as an important component of the system involved in the acquisition, storage, and expression of fear memory and has elucidated in detail how stimuli enter, travel through, and exit the amygdala. Some progress has also been made in understanding the cellular and molecular mechanisms that underlie fear conditioning, and recent studies have also shown that the findings from experimental animals apply to the human brain. It is important to remember why this work on emotion succeeded where past efforts failed. It focused on a psychologically well-defined aspect of emotion, avoided vague and poorly defined concepts such as ``affect,'' ``hedonic tone,'' or ``emotional feelings,'' and used a simple and straightforward experimental approach. With so much research being done in this area today, it is important that the mistakes of the past not be made again. It is also time to expand from this foundation into broader aspects of mind and behavior.
    BibTeX:
    @article{LeDoux2000,
      author = {LeDoux, JE},
      title = {Emotion circuits in the brain},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      publisher = {ANNUAL REVIEWS INC},
      year = {2000},
      volume = {23},
      pages = {155-184}
    }
    
    LeDoux, J. Fear and the brain: Where have we been, and where are we going? {1998} BIOLOGICAL PSYCHIATRY
    Vol. {44}({12}), pp. {1229-1238} 
    article  
    Abstract: In recent years, there has been all explosion of interest ill the neural basis of emotion. Much of this enthusiasm has been triggered by studies of the amygdala and its contribution to fear. This work has shown that the amygdala detects and organizes responses to natural dangers (like predators) and learns about novel threats and the stimuli that predict their occurrence. The latter process has been studied extensively using a procedure called classical fear conditioning. This article surveys the progress that has been made in understanding the neural basis of fear and its implications for anxiety disorders, as well as the gaps in our knowledge. Biol Psychiatry 1998;44:1229-1238 (C) 1998 Society of Biological Psychiatry.
    BibTeX:
    @article{LeDoux1998,
      author = {LeDoux, J},
      title = {Fear and the brain: Where have we been, and where are we going?},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1998},
      volume = {44},
      number = {12},
      pages = {1229-1238},
      note = {Research Symposium on Brain Neurocircuitry of Anxiety and Fear - Implications for Clinical Research and Practice, BOSTON, MASSACHUSETTS, MAR 26, 1998}
    }
    
    LEDOUX, J. EMOTION - CLUES FROM THE BRAIN {1995} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {46}, pp. {209-235} 
    article  
    BibTeX:
    @article{LEDOUX1995,
      author = {LEDOUX, JE},
      title = {EMOTION - CLUES FROM THE BRAIN},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      publisher = {ANNUAL REVIEWS INC},
      year = {1995},
      volume = {46},
      pages = {209-235}
    }
    
    LEDOUX, J. EMOTIONAL MEMORY-SYSTEMS IN THE BRAIN {1993} BEHAVIOURAL BRAIN RESEARCH
    Vol. {58}({1-2}), pp. {69-79} 
    article  
    Abstract: The neural mechanisms of emotion and memory have long been thought to reside side by side, if not in overlapping structures, of the limbic system. However, the limbic system concept is no longer acceptable as an account of the neural basis of memory or emotion and is being replaced with specific circuit accounts of specific emotional and memory processes. Emotional memory, a special category of memory involving the implicit (probably unconscious) learning and storage of information about the emotional significance of events, is modeled in rodent experiments using aversive classical conditioning techniques. The neural system underlying emotional memory critically involves the amygdala and structures with which it is connected. Afferent inputs from sensory processing areas of the thalamus and cortex mediate emotional learning in situations involving specific sensory cues, whereas learning about the emotional significance of more general, contextual cues involves projections to the amygdala from the hippocampal formation. Within the amygdala, the lateral nucleus (AL) is the sensory interface and the central nucleus the linkage with motor systems involved in the control of species-typical emotional behaviors and autonomic responses. Studies of cellular mechanisms in these pathways have focused on the direct relay to the lateral amygdala from the auditory thalamus. These studies show that single cells in AL respond to both conditioned stimulus and unconditioned stimulus inputs, leading to the notion that AL might be a critical site of sensory-sensory integration in emotional learning. The thalamo-amygdala pathway also exhibits long-term potentiation, a form of synaptic plasticity that might underlie the emotional learning functions of the circuit. The thalamo-amygdala pathway contains and uses the amino acid glutamate in synaptic transmission, suggesting the possibility that an amino-acid mediated form of synaptic plasticity is involved in the emotional learning functions of the pathway. We are thus well on the way to a systems level and a cellular understanding of at least one form of emotional learning and memory.
    BibTeX:
    @article{LEDOUX1993,
      author = {LEDOUX, JE},
      title = {EMOTIONAL MEMORY-SYSTEMS IN THE BRAIN},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1993},
      volume = {58},
      number = {1-2},
      pages = {69-79},
      note = {International Symposium on Emotion and Memory, ITATIAIA, BRAZIL, AUG 23-25, 1992}
    }
    
    LEDOUX, J., CICCHETTI, P., XAGORARIS, A. & ROMANSKI, L. THE LATERAL AMYGDALOID NUCLEUS - SENSORY INTERFACE OF THE AMYGDALA IN FEAR CONDITIONING {1990} JOURNAL OF NEUROSCIENCE
    Vol. {10}({4}), pp. {1062-1069} 
    article  
    BibTeX:
    @article{LEDOUX1990a,
      author = {LEDOUX, JE and CICCHETTI, P and XAGORARIS, A and ROMANSKI, LM},
      title = {THE LATERAL AMYGDALOID NUCLEUS - SENSORY INTERFACE OF THE AMYGDALA IN FEAR CONDITIONING},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1990},
      volume = {10},
      number = {4},
      pages = {1062-1069}
    }
    
    LEDOUX, J., FARB, C. & RUGGIERO, D. TOPOGRAPHIC ORGANIZATION OF NEURONS IN THE ACOUSTIC THALAMUS THAT PROJECT TO THE AMYGDALA {1990} JOURNAL OF NEUROSCIENCE
    Vol. {10}({4}), pp. {1043-1054} 
    article  
    BibTeX:
    @article{LEDOUX1990,
      author = {LEDOUX, JE and FARB, C and RUGGIERO, DA},
      title = {TOPOGRAPHIC ORGANIZATION OF NEURONS IN THE ACOUSTIC THALAMUS THAT PROJECT TO THE AMYGDALA},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1990},
      volume = {10},
      number = {4},
      pages = {1043-1054}
    }
    
    Lee, Y. & Davis, M. Role of the hippocampus, the bed nucleus of the stria terminalis, and the amygdala in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({16}), pp. {6434-6446} 
    article  
    Abstract: Previously, we demonstrated that transection of the fimbria/ fornix blocked the excitatory effect of corticotropin-releasing hormone (CRH) on startle (CRH-enhanced startle), suggesting that the hippocampus and its efferent target areas that communicate via the fimbria may be critically involved in CRH-enhanced startle. The bed nucleus of the stria terminalis (BNST) receives direct projections from the ventral hippocampus via the fimbria/fornix. Therefore, the role of the ventral hippocampus, the BNST, and the amygdala in CRH-enhanced startle was investigated. NMDA lesions of the BNST completely blocked CRH-enhanced startle, whereas chemical lesions of the ventral hippocampus and the amygdala failed to block CRH-enhanced startle. However, the same amygdala-lesioned animals showed a complete blockade of fear-potentiated startle, a conditioned fear response sensitive to manipulations of the amygdala. In contrast, BNST-lesioned rats had normal fear-potentiated startle. This indicates a double dissociation between the BNST and the amygdala in two different paradigms that enhance startle amplitude. Microinfusions of CRH into the BNST, but not into the ventral hippocampus, mimicked intracerebroventricular CRH effects. Furthermore, infusion of a CRH antagonist into the BNST blocked CRH-enhanced startle in a dose-dependent manner. Control studies showed that this blockade did not result from either leakage of the antagonist into the ventricular system or a local anesthetic effect caused by infusion of the antagonist into the BNST. The present studies strongly suggest that CRH in the CSF can activate the BNST, which could lead to activation of brainstem and hypothalamic BNST target areas involved in anxiety and stress responses.
    BibTeX:
    @article{Lee1997,
      author = {Lee, YL and Davis, M},
      title = {Role of the hippocampus, the bed nucleus of the stria terminalis, and the amygdala in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {16},
      pages = {6434-6446}
    }
    
    Levesque, J., Eugene, F., Joanette, Y., Paquette, V., Mensour, B., Beaudoin, G., Leroux, J., Bourgouin, P. & Beauregard, M. Neural circuitry underlying voluntary suppression of sadness {2003} BIOLOGICAL PSYCHIATRY
    Vol. {53}({6}), pp. {502-510} 
    article DOI  
    Abstract: Background: The ability to voluntarily self-regulate negative emotion is essential to a healthy psyche. Indeed, a chronic incapacity to suppress negative emotion might be a key factor in the genesis of depression and anxiety. Regarding the neural underpinnings of emotional self-regulation, a recent functional neuroimaging study carried out by our group has revealed that the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex are involved in voluntary suppression of sexual arousal. As few things are known, still, with respect to the neural substrate underlying volitional self-regulation of basic emotions, here we used functional magnetic resonance imaging to identify the neural circuitry associated with the voluntary suppression of sadness. Methods: Twenty healthy female subjects were scanned during a Sad condition and a Suppression condition. In the Sad condition, subjects were instructed to react normally to sad film excerpts whereas, in the Suppression condition, they were asked to voluntarily suppress any emotional reaction in response to comparable stimuli. Results: Transient sadness was associated with significant loci of activation in the anterior temporal pole and the midbrain, bilaterally, as well as in the left amygdala, left insula, and right ventrolateral prefrontal cortex (VLPFC) (Brodmann area [BA] 47). Correlational analyses carried out between self-report ratings of sadness and regional blood oxygen level dependent (BOLD) signal changes revealed the existence of positive correlations in the right VLPFC (BA 47), bilaterally, as well as in the left insula and the affective division of the left anterior cingulate gyrus (BA 24/32). In the Suppression condition, significant loci of activation were noted in the right DLPFC (BA 9) and the right orbitofrontal cortex (OFC) (BA 11), and positive correlations were found between the self-report ratings of sadness and BOLD signal changes in the right OFC (BA 11) and right DLPFC (BA 9). Conclusions: These results confirm the key role played by the DLPFC in emotional self-regulation. They also indicate that the right DLPFC and right OFC are components of a neural circuit implicated in voluntary suppression of sadness. (C) 2003 Society of Biological Psychiatry.
    BibTeX:
    @article{Levesque2003,
      author = {Levesque, J and Eugene, F and Joanette, Y and Paquette, V and Mensour, B and Beaudoin, G and Leroux, JM and Bourgouin, P and Beauregard, M},
      title = {Neural circuitry underlying voluntary suppression of sadness},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2003},
      volume = {53},
      number = {6},
      pages = {502-510},
      doi = {{10.1016/S0002-3223(03)01817-6}}
    }
    
    Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M., Baker, M., Yu, X., Duff, K., Hardy, J., Corral, A., Lin, W., Yen, S., Dickson, D., Davies, P. & Hutton, M. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein {2000} NATURE GENETICS
    Vol. {25}({4}), pp. {402-405} 
    article  
    Abstract: Neurofibrillary tangles (NFT) composed of the microtubule-associated protein tau are prominent in Alzheimer disease (AD), Pick disease, progressive supranuclear palsy (PSP) and corticobasal degeneration(1) (CBD). Mutations in the gene (Mtapt) encoding tau protein cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). thereby proving that tau dysfunction can directly result in neurodegeneration(2). Expression of human tau containing the most common(3-5) FTDP-17 mutation (P301L) results in motor and behavioural deficits in transgenic mice, with age- and gene-dose-dependent development of NFT. This phenotype occurred as early as 6.5 months in hemizygous and 4.5 months in homozygous animals. NFT and Pick-body-like neuronal lesions occurred in the amygdala, septal nuclei, pre-optic nuclei, hypothalamus, midbrain, pens, medulla, deep cerebellar nuclei and spinal cord, with tau-immunoreactive pre-tangles in the cortex, hippocampus and basal ganglia. Areas with the most NFT had reactive gliosis. Spinal cord had axonal spheroids, anterior horn cell toss and axonal degeneration in anterior spinal roots. We also saw peripheral neuropathy and skeletal muscle with neurogenic atrophy. Brain and spinal cord contained insoluble tau that co-migrated with insoluble tau from AD and FTDP-17 brains. The phenotype of mice expressing P301L mutant tau mimics features of human tauopathies and provides a model for investigating the pathogenesis of diseases with NFT.
    BibTeX:
    @article{Lewis2000,
      author = {Lewis, J and McGowan, E and Rockwood, J and Melrose, H and Nacharaju, P and Van Slegtenhorst, M and Gwinn-Hardy, K and Murphy, MP and Baker, M and Yu, X and Duff, K and Hardy, J and Corral, A and Lin, WL and Yen, SH and Dickson, DW and Davies, P and Hutton, M},
      title = {Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein},
      journal = {NATURE GENETICS},
      publisher = {NATURE AMERICA INC},
      year = {2000},
      volume = {25},
      number = {4},
      pages = {402-405}
    }
    
    Lewis, K., Li, C., Perrin, M., Blount, A., Kunitake, K., Donaldson, C., Vaughan, J., Reyes, T., Gulyas, J., Fischer, W., Bilezikjian, L., Rivier, J., Sawchenko, P. & Vale, W. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({13}), pp. {7570-7575} 
    article  
    Abstract: The corticotropin-releasing factor (CRF) family of neuropeptides includes the mammalian peptides CRF, urocortin, and urocortin II, as well as piscine urotensin I and frog sauvagine. The mammalian peptides signal through two G protein-coupled receptor types to modulate endocrine, autonomic, and behavioral responses to stress, as well as a range of peripheral (cardiovascular, gastrointestinal, and immune) activities. The three previously known ligands are differentially distributed anatomically and have distinct specificities for the two major receptor types. Here we describe the characterization of an additional CRF-related peptide, urocortin III. in the human and mouse. In searching the public human genome databases we found a partial expressed sequence tagged (EST) clone with significant sequence identity to mammalian and fish urocortin-related peptides. By using primers based on the human EST sequence, a full-length human clone was isolated from genomic DNA that encodes a protein that includes a predicted putative 38-aa peptide structurally related to other known family members. With a human probe, we then cloned the mouse ortholog from a genomic library. Human and mouse urocortin III share 90% identity in the 38-aa putative mature peptide. In the peptide coding region, both human and mouse urocortin III are 76% identical to pufferfish urocortin-related peptide and more distantly related to urocortin II, CRF, and urocortin from other mammalian species. Mouse urocortin III mRNA expression is found in areas of the brain including the hypothalamus, amygdala, and brainstem, but is not evident in the cerebellum, pituitary, or cerebral cortex: it is also expressed peripherally in small intestine and skin. Urocortin III is selective for type 2 CRF receptors and thus represents another potential endogenous ligand for these receptors.
    BibTeX:
    @article{Lewis2001,
      author = {Lewis, K and Li, C and Perrin, MH and Blount, A and Kunitake, K and Donaldson, C and Vaughan, J and Reyes, TM and Gulyas, J and Fischer, W and Bilezikjian, L and Rivier, J and Sawchenko, PE and Vale, WW},
      title = {Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {2001},
      volume = {98},
      number = {13},
      pages = {7570-7575}
    }
    
    LIANG, K., JULER, R. & MCGAUGH, J. MODULATING EFFECTS OF POST-TRAINING EPINEPHRINE ON MEMORY - INVOLVEMENT OF THE AMYGDALA NORADRENERGIC SYSTEM {1986} BRAIN RESEARCH
    Vol. {368}({1}), pp. {125-133} 
    article  
    BibTeX:
    @article{LIANG1986,
      author = {LIANG, KC and JULER, RG and MCGAUGH, JL},
      title = {MODULATING EFFECTS OF POST-TRAINING EPINEPHRINE ON MEMORY - INVOLVEMENT OF THE AMYGDALA NORADRENERGIC SYSTEM},
      journal = {BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1986},
      volume = {368},
      number = {1},
      pages = {125-133}
    }
    
    Lippa, C., Fujiwara, H., Mann, D., Giasson, B., Baba, M., Schmidt, M., Nee, L., O'Connell, B., Pollen, D., George-Hyslop, P., Ghetti, B., Nochlin, D., Bird, T., Cairns, N., Lee, V., Iwatsubo, T. & Trojanowski, J. Lewy bodies contain altered alpha-synuclein in brains of many familiar Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes {1998} AMERICAN JOURNAL OF PATHOLOGY
    Vol. {153}({5}), pp. {1365-1370} 
    article  
    Abstract: Missense mutations in the alpha-synuclein gene cause familial Parkinson's disease (PD), and alpha-synuclein is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease (AD). To determine whether alpha-synuclein is a component of LBs in familial AD (FAD) patients with known mutations in presenilin (n = 65) or amyloid precursor protein (n = 9) genes, studies were conducted with antibodies to alpha-, beta-, and gamma-synuclein. LBs were detected with alpha- but not beta- or gamma-synuclein antibodies in 22% of FAD brains, and alpha-synuclein-positive LBs were most numerous in amygdala where some LBs co-localized with tau-positive neurofibrillary tangles. As 12 (63 of 19 FAD amygdala samples contained alpha-synuclein-positive LBs, these inclusions may be more common in FAD brains than previously reported. Furthermore, alpha-synuclein antibodies decorated LB filaments by immunoelectron microscopy, and Western blots revealed that the solubility of alpha-synuclein was reduced compared with control brains. The presence of alpha-synuclein-positive LBs was not associated with any specific FAD mutation. These studies suggest that insoluble alpha-synuclein aggregates into filaments that form LBs in many FAD patients, and we speculate that these inclusions may compromise the function and/or viability of affected neurons in the FAD brain.
    BibTeX:
    @article{Lippa1998,
      author = {Lippa, CF and Fujiwara, H and Mann, DMA and Giasson, B and Baba, M and Schmidt, ML and Nee, LE and O'Connell, B and Pollen, DA and George-Hyslop, PS and Ghetti, B and Nochlin, D and Bird, TD and Cairns, NJ and Lee, VMY and Iwatsubo, T and Trojanowski, JQ},
      title = {Lewy bodies contain altered alpha-synuclein in brains of many familiar Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes},
      journal = {AMERICAN JOURNAL OF PATHOLOGY},
      publisher = {AMER SOC INVESTIGATIVE PATHOLOGY, INC},
      year = {1998},
      volume = {153},
      number = {5},
      pages = {1365-1370}
    }
    
    Loscher, W. Valproate: A reappraisal of its pharmacodynamic properties and mechanisms of action {1999} PROGRESS IN NEUROBIOLOGY
    Vol. {58}({1}), pp. {31-59} 
    article  
    Abstract: Valproate is currently one of the major antiepileptic drugs with efficacy for the treatment of both generalized and partial seizures in adults and children. Furthermore, the drug is increasingly used for therapy of bipolar and schizoaffective disorders, neuropathic pain and fur prophylactic treatment of migraine. These various therapeutic effects are reflected in preclinical models, including a variety of animal models of seizures or epilepsy. The incidence of toxicity associated with the clinical use of valproate is low, but two rare toxic effects, idiosyncratic fatal hepatotoxicity and teratogenicity, necessitate precautions in risk patient populations. Studies from animal models on structure-relationships indicate that the mechanisms leading to hepatotoxicity and teratogenicity are distinct and also differ from the mechanisms of anticonvulsant action of valproate. Because of its wide spectrum of anticonvulsant activity against different seizure types, it has repeatedly been suggested that valproate acts through a combination of several mechanisms. As shown in this review, there is substantial evidence that valproate increases GABA synthesis and release and thereby potentiates GABAergic functions in some specific brain regions, such as substantia nigra, thought to be involved in the control of seizure generation and propagation. Furthermore, valproate seems to reduce the release of the epileptogenic amino acid gamma-hydroxybutyric acid and to attenuate neuronal excitation induced by NMDA-type glutamate receptors. In addition to effects on amino acidergic neurotransmission; valproate exerts direct effects on excitable membranes, although the importance of this action is equivocal. Microdialysis data suggest that valproate alters dopaminergic and serotonergic functions. Valproate is metabolized to several pharmacologically active metabolites, but because of the low plasma and brain concentrations of these compounds it is not likely that they contribute significantly to the anticonvulsant and toxic effects of treatment with the parent drug. By the experimental observations summarized in this review, most clinical effects of valproate can be explained, although much remains to be learned at a number of different levels of valproate's mechanisms of action. (C) 1999 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Loscher1999,
      author = {Loscher, W},
      title = {Valproate: A reappraisal of its pharmacodynamic properties and mechanisms of action},
      journal = {PROGRESS IN NEUROBIOLOGY},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1999},
      volume = {58},
      number = {1},
      pages = {31-59}
    }
    
    LOVELL, M., EHMANN, W., BUTLER, S. & MARKESBERY, W. ELEVATED THIOBARBITURIC ACID-REACTIVE SUBSTANCES AND ANTIOXIDANT ENZYME-ACTIVITY IN THE BRAIN IN ALZHEIMERS-DISEASE {1995} NEUROLOGY
    Vol. {45}({8}), pp. {1594-1601} 
    article  
    Abstract: We determined levels of thiobarbituric acid-reactive substances (TBARS), a measure of lipid peroxidation, and the activity of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), and catalase (CAT) in the amygdala, hippocampus, pyriform cortex, superior and middle temporal gyri, inferior parietal lobule, middle frontal gyrus, occipital pole, and cerebellum of 13 Alzheimer's disease (AD) and 10 control brains. Levels of TBARS were elevated in all AD brain regions except the middle frontal gyrus, and elevation levels reached statistical significance in the hippocampus and pyriform cortex and marginal significance in the amygdala of AD subjects compared with age-matched controls. Significant; elevation of GSH-Px activity was present in AD hippocampus compared with control. Moderate but statistically insignificant elevations of GSH-Px activity also were present;in the amygdala and pyriform cortex in AD. GSSG-R activity was significantly elevated in the amygdala and hippocampus in AD subjects compared with controls. CAT activity was significantly elevated in AD hippocampus and superior and middle temporal gyri. SOD levels were elevated in all brain regions in AD patients compared with controls, although none of these elevations reached statistical significance. Antioxidant enzyme activities were significantly elevated where lipid peroxidation was most pronounced, suggesting a compensatory rise in antioxidant activity in response to increased free radical formation. This study supports the concept that; the brain in AD is under increased oxidative stress and demonstrates that the oxidative changes are most pronounced in the medial temporal lobe, where histopathologic alterations are most severe.
    BibTeX:
    @article{LOVELL1995,
      author = {LOVELL, MA and EHMANN, WD and BUTLER, SM and MARKESBERY, WR},
      title = {ELEVATED THIOBARBITURIC ACID-REACTIVE SUBSTANCES AND ANTIOXIDANT ENZYME-ACTIVITY IN THE BRAIN IN ALZHEIMERS-DISEASE},
      journal = {NEUROLOGY},
      publisher = {LITTLE BROWN CO},
      year = {1995},
      volume = {45},
      number = {8},
      pages = {1594-1601}
    }
    
    Lovell, M., Robertson, J., Teesdale, W., Campbell, J. & Markesbery, W. Copper, iron and zinc in Alzheimer's disease senile plaques {1998} JOURNAL OF THE NEUROLOGICAL SCIENCES
    Vol. {158}({1}), pp. {47-52} 
    article  
    Abstract: Concentrations of copper (Cu), iron (Fe) and zinc (Zn) were measured in the rims and cores of senile plaques (SP) and in the neuropil of the amygdala of nine Alzheimer's disease (AD) patients and in the neuropil of the amygdala of five neurologically normal control subjects using micro particle-induced X-ray emission (micro-PIXE). Comparison of SP rim and core values revealed no significant differences between levels of Cu, Fe or Zn. Zinc and Fe in SP rims and cores were significantly elevated in AD compared with AD neuropil (P<0.05). Copper was significantly elevated (P<0.05) in the rim of SP compared with AD neuropil. Comparison of AD and control neuropil revealed a significant (P<0.05) elevation of Zn in AD subjects. The elevation of these elements in SP in AD is of interest in light of the observation that Cu, Fe and particularly Zn, can accelerate aggregation of amyloid beta peptide. (C) 1998 Elsevier Science B.V.
    BibTeX:
    @article{Lovell1998,
      author = {Lovell, MA and Robertson, JD and Teesdale, WJ and Campbell, JL and Markesbery, WR},
      title = {Copper, iron and zinc in Alzheimer's disease senile plaques},
      journal = {JOURNAL OF THE NEUROLOGICAL SCIENCES},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1998},
      volume = {158},
      number = {1},
      pages = {47-52}
    }
    
    LOVENBERG, T., LIAW, C., GRIGORIADIS, D., CLEVENGER, W., CHALMERS, D., DESOUZA, E. & OLTERSDORF, T. CLONING AND CHARACTERIZATION OF A FUNCTIONALLY DISTINCT CORTICOTROPIN-RELEASING FACTOR-RECEPTOR SUBTYPE FROM RAT-BRAIN {1995} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {92}({3}), pp. {836-840} 
    article  
    Abstract: The present study reports the isolation of a cDNA clone that encodes a second member of the corticotropin-releasing factor (CRF) receptor family, designated as the CRF(2) receptor. The cDNA was identified using oligonucleotides of degenerate sequence in a PCR paradigm. A PCR fragment obtained from rat brain was utilized to isolate a full-length cDNA from a rat hypothalamus cDNA library that encoded a 411-amino acid protein with approximate to 70% identity to the known CRF(1) receptor over the entire coding region. When expressed in mouse Ltk(-) cells, this receptor stimulates cAMP production in response to CRF and known CRF-like agonists. CRF and the nonmammalian CRF-related peptides sauvagine and urotensin I stimulate adenylate cyclase activity in a dose-dependent manner with a rank order of potency different from that of the CRF(1) receptor: sauvagine > urotensin greater than or equal to rat/human CRF > ovine CRF. Tissue distribution analysis of the mRNAs by reverse transcriptase-PCR shows CRF(2) receptor mRNA is present in rat brain and detectable in lung and heart. In situ hybridization studies indicate specific expression within the brain in the ventromedial nuclei of the hypothalamus, the lateral septum, the amygdala, and entorhinal cortex, but there is unremarkable expression in the pituitary. An additional splice variant of the CRF(2) receptor with a different N-terminal domain has been identified by PCR, encoding a putative protein of 431 amino acids. Thus, the data demonstrate the presence of another functional CRF receptor, with significant differences in the pharmacological profile and tissue distribution from the CRF(1) receptor, which would predict important functional differences between the two receptors.
    BibTeX:
    @article{LOVENBERG1995,
      author = {LOVENBERG, TW and LIAW, CW and GRIGORIADIS, DE and CLEVENGER, W and CHALMERS, DT and DESOUZA, EB and OLTERSDORF, T},
      title = {CLONING AND CHARACTERIZATION OF A FUNCTIONALLY DISTINCT CORTICOTROPIN-RELEASING FACTOR-RECEPTOR SUBTYPE FROM RAT-BRAIN},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1995},
      volume = {92},
      number = {3},
      pages = {836-840}
    }
    
    Lowe, M., Mock, B. & Sorenson, J. Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations {1998} NEUROIMAGE
    Vol. {7}({2}), pp. {119-132} 
    article  
    Abstract: A previous report of correlations in low-frequency resting-state fluctuations between right and left hemisphere motor cortices in rapidly sampled single-slice echoplanar data is confirmed using a whole-body echoplanar MRI scanner at 1.5 T. These correlations are extended to lower sampling rate multislice echoplanar acquisitions and other right/left hemisphere-symmetric functional cortices. The specificity of the correlations in the lower sampling-rate acquisitions is lower due to cardiac and respiratory-cycle effects which are aliased into the pass-band of the low-pass filter. Data are combined for three normal right-handed male subjects. Correlations to left hemisphere motor cortex, visual cortex, and amygdala are measured in long resting-state scans. (C) 1998 Academic Press.
    BibTeX:
    @article{Lowe1998,
      author = {Lowe, MJ and Mock, BJ and Sorenson, JA},
      title = {Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations},
      journal = {NEUROIMAGE},
      publisher = {ACADEMIC PRESS INC},
      year = {1998},
      volume = {7},
      number = {2},
      pages = {119-132},
      note = {2nd International Conference on Functional Mapping of the Human Brain, BOSTON, MASSACHUSETTS, JUN 17-21, 1996}
    }
    
    MacQueen, G., Campbell, S., McEwen, B., MacDonald, K., Amano, S., Joffe, R., Nahmias, C. & Young, L. Course of illness, hippocampal function, and hippocampal volume in major depression {2003} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {100}({3}), pp. {1387-1392} 
    article DOI  
    Abstract: Studies have examined hippocampal function and volume in depressed subjects, but none have systematically compared never-treated first-episode patients with those who have had multiple episodes. We sought to compare hippocampal function, as assessed by performance on hippocampal-dependent recollection memory tests, and hippocampal volumes, as measured in a 1.5-T magnetic resonance imager, in depressed subjects experiencing a postpubertal onset of depression. Twenty never-treated depressed subjects in a first episode of depression were compared with matched healthy control subjects. Seventeen depressed subjects with multiple past episodes of depression were also compared with matched healthy controls and to the first-episode patients. Both first- and multiple-episode depressed groups had hippocampal dysfunction apparent on several tests of recollection memory; only depressed subjects with multiple depressive episodes had hippocampal volume reductions. Curve-fitting analysis revealed a significant logarithmic association between illness duration and hippocampal volume. Reductions in hippocampal volume may not antedate illness onset, but volume may decrease at the greatest rate in the early years after illness onset.
    BibTeX:
    @article{MacQueen2003,
      author = {MacQueen, GM and Campbell, S and McEwen, BS and MacDonald, K and Amano, S and Joffe, RT and Nahmias, C and Young, LT},
      title = {Course of illness, hippocampal function, and hippocampal volume in major depression},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {2003},
      volume = {100},
      number = {3},
      pages = {1387-1392},
      doi = {{10.1073/pnas.0337481100}}
    }
    
    MAILLEUX, P. & VANDERHAEGHEN, J. DISTRIBUTION OF NEURONAL CANNABINOID RECEPTOR IN THE ADULT-RAT BRAIN - A COMPARATIVE RECEPTOR-BINDING AUTORADIOGRAPHY AND INSITU HYBRIDIZATION HISTOCHEMISTRY {1992} NEUROSCIENCE
    Vol. {48}({3}), pp. {655-668} 
    article  
    Abstract: The neuronal distribution of cannabinoid receptor in the adult rat brain is reported, combining receptor binding radioautography using the synthetic psychoative cannabinoid ligand CP55,940 with in situ hybridization histochemistry using oligonucleotide probes complementary to rat cannabinoid receptor cDNA. In the cerebral cortex, especially in the frontal and cingulate cortex, dense binding was found in layers I and VI together with slight mRNA levels in a majority of both pyramidal and non-pyramidal-shaped neurons and of high mRNA levels in a moderate number of non-pyramidal-shaped neurons especially in layers II-III and V-VI. In the hippocampal dentate gyrus, very dense staining was found in the molecular layer together with high mRNA levels in a moderate number of hilar neurons close to the granular layer. In Ammon's horn, especially in the CA3 sector, very dense binding was found in the dendritic layers together with slight mRNA levels in the majority of the pyramidal cells and high mRNA levels in a moderate number of interneurons. In the basal ganglia, binding was very dense in the lateral putamen, substantia nigra pars reticulata, globus pallidus and entopeduncular nucleus, moderate in the medial putamen and caudate; and slight in the accumbens, together with slight to moderate mRNA levels in the striatal medium-sized neurons. Together with slight binding, slight to moderate mRNA levels were found in the majority of the neurons in the subthalamic nucleus. No binding and mRNA were found in the substantia nigra pars compacta and ventral tegmental area. Slight to moderate binding was found together with slight to moderate mRNA levels in the majority of neurons in the anterior olfactory nucleus; septum, especially medial septum and diagonal band of Broca; amygdala, especially basolateral amygdala; lateral habenula; ventromedial hypothalamic nucleus; lateral interpenduncular nucleus; central gray, dorsal cochlear nucleus; parabrachial nucleus; dorsal pontine tegmentum; pontine nuclei; commissural part of the nucleus tractus solitarius; inferior olive and dorsal horn of the spinal cord. In the cerebellum, very dense binding was found in the molecular layer together with slight mRNA levels in the majority of the granule cells and moderate mRNA levels in the basket and stellate cells. In conclusion, this study provides, for the first time, indirect assessment of the neurons containing cannabinoid receptor in the entire adult rat brain and will serve as a basis for future direct morphological confirmation using receptor immunohistochemistry and for functional studies.
    BibTeX:
    @article{MAILLEUX1992,
      author = {MAILLEUX, P and VANDERHAEGHEN, JJ},
      title = {DISTRIBUTION OF NEURONAL CANNABINOID RECEPTOR IN THE ADULT-RAT BRAIN - A COMPARATIVE RECEPTOR-BINDING AUTORADIOGRAPHY AND INSITU HYBRIDIZATION HISTOCHEMISTRY},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1992},
      volume = {48},
      number = {3},
      pages = {655-668}
    }
    
    MALDONADO, R., STINUS, L., GOLD, L. & KOOB, G. ROLE OF DIFFERENT BRAIN STRUCTURES IN THE EXPRESSION OF THE PHYSICAL MORPHINE-WITHDRAWAL SYNDROME {1992} JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
    Vol. {261}({2}), pp. {669-677} 
    article  
    Abstract: The aim of this study was to investigate the neuroanatomical regions implicated in the expression of the physical signs of morphine withdrawal by using local intracerebral injections of methylnaloxonium in dependent rats. Guide cannulas were implanted and aimed at the lateral ventricle, nucleus accumbens, central amygdala, anterior hypothalamus, medial thalamus, periaqueductal gray matter, locus coeruleus and nucleus raphe magnus. After surgery, rats were made physically dependent by s.c. implantation of two 75-mg morphine pellets. Methylnaloxonium, a quaternary derivative of naloxone (31-1000 ng), was administered 72 hr after pellet implantation. Methylnaloxonium administered i.c.v. induced a withdrawal syndrome similar to systemic naloxone, although several signs such as diarrhea, salivation, lacrimation and rhinorrhea did not appear, suggesting possible peripheral mediation. The most sensitive site for methylnaloxonium-precipitated withdrawal was the locus coeruleus. Signs such as jumping, rearing and locomotor activity were particularly frequent after methylnaloxonium injections into the locus coeruleus. Rearing and locomotor activity were also strongly increased after methylnaloxonium administration into the periaqueductal gray matter. Wet dog shakes were mainly observed after methylnaloxonium administration into the anterior preoptic hypothalamus and nucleus raphe magnus. Injections of methylnaloxonium into the amygdala produced a weak withdrawal syndrome, and the nucleus accumbens and medial thalamus were the least sensitive structures. These results suggest that the locus coeruleus, and secondarily the periaqueductal gray matter, play an important role in the precipitation of the physical signs of opiate withdrawal, mainly in the expression of its motor component. The expression of other signs of withdrawal appear to be multisite determined.
    BibTeX:
    @article{MALDONADO1992,
      author = {MALDONADO, R and STINUS, L and GOLD, LH and KOOB, GF},
      title = {ROLE OF DIFFERENT BRAIN STRUCTURES IN THE EXPRESSION OF THE PHYSICAL MORPHINE-WITHDRAWAL SYNDROME},
      journal = {JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS},
      publisher = {WILLIAMS & WILKINS},
      year = {1992},
      volume = {261},
      number = {2},
      pages = {669-677}
    }
    
    MANSOUR, A., FOX, C., BURKE, S., AKIL, H. & WATSON, S. IMMUNOHISTOCHEMICAL LOCALIZATION OF THE CLONED MU-OPIOID RECEPTOR IN THE RAT CNS {1995} JOURNAL OF CHEMICAL NEUROANATOMY
    Vol. {8}({4}), pp. {283-305} 
    article  
    Abstract: Three opioid receptor types have recently been cloned that correspond to the pharmacologically defined mu, delta and K-1 receptors. In situ hybridization studies suggest that the opioid receptor mRNAs that encode these receptors have distinct distributions in the central nervous system that correlate well with their known functions. In the present study polyclonal antibodies were generated to the C terminal 63 amino acids of the cloned mu receptor (335-398) to examine the distribution of the mu receptor-like protein with immunohistochemical techniques. mu receptor-like immunoreactivity is widely distributed in the rat central nervous system with immunoreactive fibers and/or perikarya in such regions as the neocortex, the striatal patches and subcallosal streak, nucleus accumbens, lateral and medial septum, endopiriform nucleus, globus pallidus and ventral pallidum, amygdala, hippocampus, presubiculum, thalamic and hypothalamic nuclei, superior and inferior colliculi, central grey, substantia nigra, ventral tegmental area, interpeduncular nucleus, medial terminal nucleus of the accessory optic tract, raphe nuclei, nucleus of the solitary tract, spinal trigeminal nucleus, dorsal motor nucleus of vagus, the spinal cord and dorsal root ganglia. In addition, two major neuronal pathways, the fasciculus retroflexus and the stria terminalis, exhibit densely stained axonal fibers. While this distribution is in excellent agreement with the known mu receptor binding localization, a few regions, such as neocortex and cingulate cortex, basolateral amygdala, medial geniculate nucleus and the medial preoptic area fail to show a good correspondence. Several explanations are provided to interpret these results, and the anatomical and functional implications of these findings are discussed.
    BibTeX:
    @article{MANSOUR1995,
      author = {MANSOUR, A and FOX, CA and BURKE, S and AKIL, H and WATSON, SJ},
      title = {IMMUNOHISTOCHEMICAL LOCALIZATION OF THE CLONED MU-OPIOID RECEPTOR IN THE RAT CNS},
      journal = {JOURNAL OF CHEMICAL NEUROANATOMY},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1995},
      volume = {8},
      number = {4},
      pages = {283-305}
    }
    
    MANSOUR, A., FOX, C., BURKE, S., MENG, F., THOMPSON, R., AKIL, H. & WATSON, S. MU-OPIOID, DELTA-OPIOID, AND KAPPA-OPIOID RECEPTOR MESSENGER-RNA EXPRESSION IN THE RAT CNS - AN IN-SITU HYBRIDIZATION STUDY {1994} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {350}({3}), pp. {412-438} 
    article  
    Abstract: The mu, delta, and kappa opioid receptors are the three main types of opioid receptors found in the central nervous system (CNS) and periphery. These receptors and the peptides with which they interact are important in a number of physiological functions, including analgesia, respiration, and hormonal regulation. This study examines the expression of mu, delta, and kappa receptor mRNAs in the rat brain and spinal cord using in situ hybridization techniques. Tissue sections were hybridized with S-35-labeled cRNA probes to the rat mu (744-1,064 b), delta (304-1,287 b), and kappa (1,351-2,124 b) receptors. Each mRNA demonstrates a distinct anatomical distribution that corresponds well to known receptor binding distributions. Cells expressing mu receptor mRNA are localized in such regions as the olfactory bulb, caudate-putamen, nucleus accumbens, lateral and medial septum, diagonal band of Broca, bed nucleus of the stria terminalis, most thalamic nuclei, hippocampus, amygdala, medial preoptic area, superior and inferior colliculi, central gray, dorsal and median raphe, raphe magnus, locus coeruleus, parabrachial nucleus, pontine and medullary reticular nuclei, nucleus ambiguus, nucleus of the solitary tract, nucleus gracilis and cuneatus, dorsal motor nucleus of vagus, spinal cord, and dorsal root ganglia. Cellular localization of delta receptor mRNA varied from mu, or kappa, with expression in such regions as the olfactory bulb, allo- and neocortex, caudate-putamen, nucleus accumbens, olfactory tubercle, ventromedial hypothalamus, hippocampus, amygdala, red nucleus, pontine nuclei, reticulotegmental nucleus, motor and spinal trigeminal, linear nucleus of the medulla, lateral reticular nucleus, spinal cord, and dorsal root ganglia. Cells expressing kappa receptor mRNA demonstrate a third pattern of expression, with cells localized in regions such as the claustrum, endopiriform nucleus, nucleus accumbens, olfactory tubercle, medial preoptic area, bed nucleus of the stria terminalis, amygdala, most hypothalamic nuclei, median eminence, infundibulum, substantia nigra, ventral tegmental area, raphe nuclei, paratrigeminal and spinal trigeminal, nucleus of the solitary tract, spinal cord, and dorsal root ganglia. These findings are discussed in relation to the physiological functions associated with the opioid receptors. (C) 1994 Wiley-Liss, Inc.
    BibTeX:
    @article{MANSOUR1994,
      author = {MANSOUR, A and FOX, CA and BURKE, S and MENG, F and THOMPSON, RC and AKIL, H and WATSON, SJ},
      title = {MU-OPIOID, DELTA-OPIOID, AND KAPPA-OPIOID RECEPTOR MESSENGER-RNA EXPRESSION IN THE RAT CNS - AN IN-SITU HYBRIDIZATION STUDY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1994},
      volume = {350},
      number = {3},
      pages = {412-438}
    }
    
    MANSOUR, A., FOX, C., THOMPSON, R., AKIL, H. & WATSON, S. MU-OPIOID RECEPTOR MESSENGER-RNA EXPRESSION IN THE RAT CNS - COMPARISON TO MU-RECEPTOR BINDING {1994} BRAIN RESEARCH
    Vol. {643}({1-2}), pp. {245-265} 
    article  
    Abstract: The distribution of cells expressing mu-receptor mRNA and mu-receptor binding sites were compared in brain and spinal cord tissue sections using a combination of in situ hybridization and receptor autoradiographic techniques. mu-Receptor mRNA was visualized with a S-35-labeled cRNA probe directed to transmembrane III-VI of the rat mu-receptor, while mu-receptor binding sites were labeled with the mu-selective ligand [H-3]DAMGO. A high correspondence between the mu-receptor mRNA and receptor binding distributions was observed in the nucleus of the accessory olfactory bulb, anterior olfactory nuclei, striatal patches of the nucleus accumbens and caudate-putamen, endopiriform nucleus, claustrum, diagonal band of Broca, globus pallidus, ventral pallidum, bed nucleus of stria terminalis, most thalamic nuclei, medial and posteriocortical medial amygdala, lateral, dorsomedial, posterior and mammillary nuclei of the hypothalamus, presubiculum, subiculum, rostral interpeduncular nucleus, median raphe, inferior colliculus, parabrachial nucleus, locus coeruleus, central grey, nucleus ambiguus, nucleus of the solitary tract, nucleus gracilis, nucleus cuneatus, and the dorsal motor nucleus of vagus. Differences in mu-receptor mRNA and receptor binding distributions were observed in several regions, including the olfactory bulb, cortex, hippocampus, superior colliculus, spinal trigeminal nucleus, cochlear nucleus and spinal cord, and may be due to mu-receptor transport to presynaptic terminals.
    BibTeX:
    @article{MANSOUR1994a,
      author = {MANSOUR, A and FOX, CA and THOMPSON, RC and AKIL, H and WATSON, SJ},
      title = {MU-OPIOID RECEPTOR MESSENGER-RNA EXPRESSION IN THE RAT CNS - COMPARISON TO MU-RECEPTOR BINDING},
      journal = {BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1994},
      volume = {643},
      number = {1-2},
      pages = {245-265}
    }
    
    Maquet, P., Peters, J., Aerts, J., Delfiore, G., Degueldre, C., Luxen, A. & Franck, G. Functional neuroanatomy of human rapid-eye-movement sleep and dreaming {1996} NATURE
    Vol. {383}({6596}), pp. {163-166} 
    article  
    Abstract: RAPID-EYE-MOVEMENT (REM) sleep is associated with intense neuronal activity, ocular saccades, muscular atonia and dreaming(1,2). The function of REM sleep remains elusive and its neural correlates have not been characterized precisely in man. Here we use positron emission tomography and statistical parametric mapping to study the brain state associated with REM sleep in humans. We report a group study of seven subjects who maintained steady REM sleep during brain scanning and recalled dreams upon awakening. The results show that regional cerebral blood flow is positively correlated with REM sleep in pontine tegmentum, left thalamus, both amygdaloid complexes, anterior cingulate cortex and right parietal operculum. Negative correlations between regional cerebral blood flow and REM sleep are observed bilaterally, in a vast area of dorsolateral prefrontal cortex, in parietal cortex (supramarginal gyrus) as well as in posterior cingulate cortex and precuneus. Given the role of the amygdaloid complexes in the acquisition of emotionally influenced memories, the pattern of activation in the amygdala and the cortical areas provides a biological basis for the processing of some types of memory during REM sleep.
    BibTeX:
    @article{Maquet1996,
      author = {Maquet, P and Peters, JM and Aerts, J and Delfiore, G and Degueldre, C and Luxen, A and Franck, G},
      title = {Functional neuroanatomy of human rapid-eye-movement sleep and dreaming},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1996},
      volume = {383},
      number = {6596},
      pages = {163-166}
    }
    
    Maren, S. Neurobiology of Pavlovian fear conditioning {2001} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {24}, pp. {897-931} 
    article  
    Abstract: Learning the relationships between aversive events and the environmental stimuli that predict such events is essential to the survival of organisms throughout the animal kingdom. Pavlovian fear conditioning is an exemplar of this form of learning that is exhibited by both rats and humans. Recent years have seen an incredible surge in interest in the neurobiology of fear conditioning. Neural circuits underlying fear conditioning have been mapped, synaptic plasticity in these circuits has been identified, and biochemical and genetic manipulations are beginning to unravel the molecular machinery responsible for the storage of fear memories. These advances represent an important step in understanding the neural substrates of a rapidly acquired and adaptive form of associative learning and memory in mammals.
    BibTeX:
    @article{Maren2001,
      author = {Maren, S},
      title = {Neurobiology of Pavlovian fear conditioning},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      publisher = {ANNUAL REVIEWS},
      year = {2001},
      volume = {24},
      pages = {897-931}
    }
    
    Maren, S., Aharonov, G. & Fanselow, M. Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats {1997} BEHAVIOURAL BRAIN RESEARCH
    Vol. {88}({2}), pp. {261-274} 
    article  
    Abstract: Electrolytic lesions of the dorsal hippocampus (DH) produce deficits in both the acquisition and expression of conditional fear to contextual stimuli in rats. To assess whether damage to DH neurons is responsible for these deficits, we performed three experiments to examine the effects of neurotoxic N-methyl-D-aspartate (NMDA) lesions of the DH on the acquisition and expression of fear conditioning. Fear conditioning consisted of the delivery of signaled or unsignaled footshocks in a novel conditioning chamber and freezing served as the measure of conditional fear. In Experiment 1, posttraining DH lesions produced severe retrograde deficits in context fear when made either 1 or 28, but not 100, days following training. Pretraining DH lesions made 1 week before training did not affect contextual fear conditioning. Tone fear was impaired by DH lesions at all training-to-lesion intervals. In Experiment 2, posttraining (1 day), but not pretraining (1 week), DH lesions produced substantial deficits in context fear using an unsignaled shock procedure. In Experiment 3, pretraining electrolytic DH lesions produced modest deficits in context fear using the same signaled and unsignaled shock procedures used in Experiments I and 2, respectively. Electrolytic, but not neurotoxic, lesions also increased pre-shock locomotor activity. Collectively, this pattern of results reveals that neurons in the DH are not required for the acquisition of context fear, but have a critical and time-limited role in the expression of context fear. The normal acquisition and expression of context fear in rats with neurotoxic DH lesions made before training may be mediated by conditioning to unimodal cues in the context, a process that may rely less on the hippocampal memory system. (C) 1997 Elsevier Science B.V.
    BibTeX:
    @article{Maren1997,
      author = {Maren, S and Aharonov, G and Fanselow, MS},
      title = {Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1997},
      volume = {88},
      number = {2},
      pages = {261-274}
    }
    
    Maren, S., Aharonov, G., Stote, D. & Fanselow, M. N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats {1996} BEHAVIORAL NEUROSCIENCE
    Vol. {110}({6}), pp. {1365-1374} 
    article  
    Abstract: Three experiments examined the effects of intra-amygdaloid infusions of an N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), on contextual fear conditioning in rats. In Experiment 1, APV infusion into the basolateral amygdala (BLA), before training, disrupted the acquisition of contextual fear. In Experiment 2, APV produced a disruption of both the acquisition and expression of contextual fear. This blockade of contextual fear was not state dependent, not due to a shift in footshock sensitivity, and not the result of increased motor activity in APV-treated rats. In Experiment 3, fear conditioning was not affected by a posttraining APV infusion into the BLA. These results indicate that NMDA receptors in the BLA are necessary for both the acquisition and expression of Pavlovian fear conditioning to contextual cues in rats.
    BibTeX:
    @article{Maren1996,
      author = {Maren, S and Aharonov, G and Stote, DL and Fanselow, MS},
      title = {N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats},
      journal = {BEHAVIORAL NEUROSCIENCE},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1996},
      volume = {110},
      number = {6},
      pages = {1365-1374}
    }
    
    MAREN, S. & FANSELOW, M. SYNAPTIC PLASTICITY IN THE BASOLATERAL AMYGDALA INDUCED BY HIPPOCAMPAL-FORMATION STIMULATION IN-VIVO {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({11}), pp. {7548-7564} 
    article  
    Abstract: Several studies suggest that axonal projections from the hippocampal formation (HF) to the basolateral amygdala (BLA) play a role in Pavlovian fear conditioning to contextual conditional stimuli, We have used electrophysiological techniques to characterize neuronal transmission in these projections in urethane-anesthetized rats. Single-pulse electrical stimulation of the ventral angular bundle (VAB), which carries projections from the HF to the BLA, reliably evoked a biphasic extracellular field potential in the BLA that consisted of an early, negative and a late, positive component. The negative component of the field potential occurred at a short latency (3-8 msec), was both temporally and spatially correlated with VAB-evoked multiple-unit discharges in the BLA, and exhibited properties typical of a monosynaptic response, Infusion of lidocaine or glutamate receptor antagonists into the BLA attenuated VAB-evoked field potentials, indicating that they are generated by local synaptic glutamatergic transmission, Both paired-pulse stimulation and brief trains of high-frequency stimulation (HFS) induced a short-lasting facilitation of BLA field potentials, whereas longer and more numerous trains of HFS produced an enduring, NMDA receptor-dependent long-term potentiation (LTP) of the potentials, The induction of LTP was accompanied by a decrease in paired-pulse facilitation (PPF), suggesting a presynaptic modification underlying its expression, Electrolytic lesions placed in regions of the HF that project to the BLA or excitotoxic lesions placed in the BLA eliminated Pavlovian fear conditioning to a contextual conditional stimulus. The critical role of both structures in context conditioning implicates plasticity at HF-BLA synapses in this form of learning.
    BibTeX:
    @article{MAREN1995,
      author = {MAREN, S and FANSELOW, MS},
      title = {SYNAPTIC PLASTICITY IN THE BASOLATERAL AMYGDALA INDUCED BY HIPPOCAMPAL-FORMATION STIMULATION IN-VIVO},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1995},
      volume = {15},
      number = {11},
      pages = {7548-7564}
    }
    
    Maren, S. & Quirk, G. Neuronal signalling of fear memory {2004} NATURE REVIEWS NEUROSCIENCE
    Vol. {5}({11}), pp. {844-852} 
    article DOI  
    Abstract: The learning and remembering of fearful events depends on the integrity of the amygdala, but how are fear memories represented in the activity of amygdala neurons? Here, we review recent electrophysiological studies indicating that neurons in the lateral amygdala encode aversive memories during the acquisition and extinction of Pavlovian fear conditioning. Studies that combine unit recording with brain lesions and pharmacological inactivation provide evidence that the lateral amygdala is a crucial locus of fear memory. Extinction of fear memory reduces associative plasticity in the lateral amygdala and involves the hippocampus and prefrontal cortex. Understanding the signalling of aversive memory by amygdala neurons opens new avenues for research into the neural systems that support fear behaviour.
    BibTeX:
    @article{Maren2004,
      author = {Maren, S and Quirk, GJ},
      title = {Neuronal signalling of fear memory},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2004},
      volume = {5},
      number = {11},
      pages = {844-852},
      doi = {{10.1038/nrn1535}}
    }
    
    Markesbery, W. & Lovell, M. Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease {1998} NEUROBIOLOGY OF AGING
    Vol. {19}({1}), pp. {33-36} 
    article  
    Abstract: Recent studies have implicated increased oxidative stress in the pathogenesis of Alzheimer's disease (AD). Increased lipid peroxidation and decreased polyunsaturated fatty acid levels have been described in the brain in AD. Four-hydroxynonenal (HNE), an aldehyde product of lipid peroxidation, has been demonstrated to be a neurotoxin in tissue culture and in vivo studies and is elevated in ventricular fluid in AD. We report here an increase in mean free HNE in multiple brain regions in AD compared with age-matched control subjects. These increases reached statistical significance in the amygdala and hippocampus and parahippocampal gyrus, regions showing the most pronounced histopathological alterations in AD. This study, in conjunction with cell culture studies, suggests that HNE may be an important substance in the pathogenesis of neuron degeneration in AD. (C) 1998 Elsevier Science Inc.
    BibTeX:
    @article{Markesbery1998,
      author = {Markesbery, WR and Lovell, MA},
      title = {Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease},
      journal = {NEUROBIOLOGY OF AGING},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1998},
      volume = {19},
      number = {1},
      pages = {33-36}
    }
    
    Marsicano, G. & Lutz, B. Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain {1999} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {11}({12}), pp. {4213-4225} 
    article  
    Abstract: Cannabinoids can modulate motor behaviour, learning and memory, cognition and pain perception. These effects correlate with the expression of the cannabinoid receptor 1 (CB1) and with the presence of endogenous cannabinoids in the brain. In trying to obtain further insights into the mechanisms underlying the modulatory effects of cannabinoids, CB1-positive neurons were determined in the murine forebrain at a single cell resolution. We performed a double in situ hybridization study to detect mRNA of CB1 in combination with mRNA of glutamic acid decarboxylase 65k, neuropeptide cholecystokinin (CCK), parvalbumin, calretinin and calbindin D28k, respectively. Our results revealed that CB1-expressing cells can be divided into distinct neuronal subpopulations. There is a clear distinction between neurons containing CB1 mRNA either at high levels or low levels. The majority of high CB1-expressing cells are GABAergic (gamma-aminobutyric acid) neurons belonging mainly to the cholecystokinin-positive and parvalbumin-negative type of interneurons (basket cells) and, to a lower extent, to the calbindin D28k-positive mid-proximal dendritic inhibitory interneurons. Only a fraction of low CB1-expressing cells is GABAergic. In the hippocampus, amygdala and entorhinal cortex area, CB1 mRNA is present at low but significant levels in many non-GABAergic cells that can be considered as projecting principal neurons. Thus, a complex mechanism appears to underlie the modulatory effects of cannabinoids. They might act on principal glutamatergic circuits as well as modulate local GABAergic inhibitory circuits. CB1 is very highly coexpressed with CCK. It is known that cannabinoids and CCK often have opposite effects on behaviour and physiology. Therefore, we suggest that a putative cross-talk between cannabinoids and CCK might exist and will be relevant to better understanding of physiology and pharmacology of the cannabinoid system.
    BibTeX:
    @article{Marsicano1999,
      author = {Marsicano, G and Lutz, B},
      title = {Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      publisher = {BLACKWELL SCIENCE LTD},
      year = {1999},
      volume = {11},
      number = {12},
      pages = {4213-4225}
    }
    
    Marsicano, G., Wotjak, C., Azad, S., Bisogno, T., Rammes, G., Cascio, M., Hermann, H., Tang, J., Hofmann, C., Zieglgansberger, W., Di Marzo, V. & Lutz, B. The endogenous cannabinoid system controls extinction of aversive memories {2002} NATURE
    Vol. {418}({6897}), pp. {530-534} 
    article DOI  
    Abstract: Acquisition and storage of aversive memories is one of the basic principles of central nervous systems throughout the animal kingdom(1). In the absence of reinforcement, the resulting behavioural response will gradually diminish to be finally extinct. Despite the importance of extinction(2), its cellular mechanisms are largely unknown. The cannabinoid receptor 1 (CB1)(3) and endocannabinoids(4) are present in memory-related brain areas(5,6) and modulate memory(7,8). Here we show that the endogenous cannabinoid system has a central function in extinction of aversive memories. CB1-deficient mice showed strongly impaired short-term and long-term extinction in auditory fear-conditioning tests, with unaffected memory acquisition and consolidation. Treatment of wild-type mice with the CB1 antagonist SR141716A mimicked the phenotype of CB1-deficient mice, revealing that CB1 is required at the moment of memory extinction. Consistently, tone presentation during extinction trials resulted in elevated levels of endocannabinoids in the basolateral amygdala complex,a region known to control extinction of aversive memories(9). In the basolateral amygdala, endocannabinoids and CB1 were crucially involved in long-term depression of GABA (gamma-aminobutyric acid)-mediated inhibitory currents. We propose that endocannabinoids facilitate extinction of aversive memories through their selective inhibitory effects on local inhibitory networks in the amygdala.
    BibTeX:
    @article{Marsicano2002,
      author = {Marsicano, G and Wotjak, CT and Azad, SC and Bisogno, T and Rammes, G and Cascio, MG and Hermann, H and Tang, JR and Hofmann, C and Zieglgansberger, W and Di Marzo, V and Lutz, B},
      title = {The endogenous cannabinoid system controls extinction of aversive memories},
      journal = {NATURE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2002},
      volume = {418},
      number = {6897},
      pages = {530-534},
      doi = {{10.1038/nature00839}}
    }
    
    Marti, H., Wenger, R., Rivas, L., Straumann, U., Digicaylioglu, M., Henn, V., Yonekawa, Y., Bauer, C. & Gassmann, M. Erythropoietin gene expression in human, monkey and murine brain {1996} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {8}({4}), pp. {666-676} 
    article  
    Abstract: The haematopoietic growth factor erythropoietin is the primary regulator of mammalian erythropoiesis and is produced by the kidney and the liver in an oxygen-dependent manner. We and others have recently demonstrated erythropoietin gene expression in the rodent brain. In this work, we show that cerebral erythropoietin gene expression is not restricted to rodents but occurs also in the primate brain. Erythropoietin mRNA was detected in biopsies from the human hippocampus, amygdala and temporal cortex and in various brain areas of the monkey Macaca mulatta. Exposure to a low level of oxygen led to elevated erythropoietin mRNA levels in the monkey brain, as did anaemia in the mouse brain. In addition, erythropoietin receptor mRNA was detected in all brain biopsies tested from man, monkey and mouse. Analysis of primary cerebral cells isolated from newborn mice revealed that astrocytes, but not microglia cells, expressed erythropoietin. When incubated at 1% oxygen, astrocytes showed >100-fold time-dependent erythropoietin mRNA accumulation, as measured with the quantitative reverse transcription-polymerase chain reaction. The specificity of hypoxic gene induction in these cells was confirmed by quantitative Northern blot analysis showing hypoxic up-regulation of mRNA encoding the vascular endothelial growth factor, but not of other genes. These findings demonstrate that erythropoietin and its receptor are expressed in the brain of primates as they are in rodents, and that, at least in mice, primary astrocytes are a source of cerebral erythropoietin expression which can be up-regulated by reduced oxygenation.
    BibTeX:
    @article{Marti1996,
      author = {Marti, HH and Wenger, RH and Rivas, LA and Straumann, U and Digicaylioglu, M and Henn, V and Yonekawa, Y and Bauer, C and Gassmann, M},
      title = {Erythropoietin gene expression in human, monkey and murine brain},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS UNITED KINGDOM},
      year = {1996},
      volume = {8},
      number = {4},
      pages = {666-676}
    }
    
    MARTIN, L., BLACKSTONE, C., HUGANIR, R. & PRICE, D. CELLULAR-LOCALIZATION OF A METABOTROPIC GLUTAMATE RECEPTOR IN RAT-BRAIN {1992} NEURON
    Vol. {9}({2}), pp. {259-270} 
    article  
    Abstract: In rat brain, the cellular localization of a phosphoinositide-linked metabotropic glutamate receptor(mGluR1-alpha) was demonstrated using antibodies that recognize the C-terminus of the receptor. mGluR1-alpha, a 142 kd protein, is enriched within the olfactory bulb, stratum oriens of CA1 and polymorph layer of dentate gyrus in hippocampus, globus pallidus, thalamus, substantia nigra, superior colliculus, and cerebellum. Lower levels of mGluR1-alpha are present within neocortex, striatum, amygdala, hypothalamus, and medulla. Dendrites, spines, and neuronal cell bodies contain mGluR1-alpha. mGluR1-alpha is not detectable in presynaptic terminals. mGluR1-alpha and ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits show differential distributions, but in Purkinje cells, mGluR1-alpha and specific AMPA receptor subunits colocalize. The postsynaptic distribution of mGluR1-alpha is consistent with postulated physiological roles of this subtype of glutamate receptor.
    BibTeX:
    @article{MARTIN1992,
      author = {MARTIN, LJ and BLACKSTONE, CD and HUGANIR, RL and PRICE, DL},
      title = {CELLULAR-LOCALIZATION OF A METABOTROPIC GLUTAMATE RECEPTOR IN RAT-BRAIN},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {1992},
      volume = {9},
      number = {2},
      pages = {259-270}
    }
    
    Martin, S., Grimwood, P. & Morris, R. Synaptic plasticity and memory: An evaluation of the hypothesis {2000} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {23}, pp. {649-711} 
    article  
    Abstract: Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. In its most general form, the synaptic plasticity and memory hypothesis states that ``activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed.'' We outline a set of criteria by which this hypothesis can be judged and describe a range of experimental strategies used to investigate it. We review both classical and newly discovered properties of synaptic plasticity and stress the importance of the neural architecture and synaptic learning rules of the network in which it is embedded. The greater part of the article focuses on types of memory mediated by the hippocampus, amygdala, and cortex. We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.
    BibTeX:
    @article{Martin2000,
      author = {Martin, SJ and Grimwood, PD and Morris, RGM},
      title = {Synaptic plasticity and memory: An evaluation of the hypothesis},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      publisher = {ANNUAL REVIEWS INC},
      year = {2000},
      volume = {23},
      pages = {649-711}
    }
    
    MASTERS, B., QUAIFE, C., ERICKSON, J., KELLY, E., FROELICK, G., ZAMBROWICZ, B., BRINSTER, R. & PALMITER, R. METALLOTHIONEIN-III IS EXPRESSED IN NEURONS THAT SEQUESTER ZINC IN SYNAPTIC VESICLES {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({10}), pp. {5844-5857} 
    article  
    Abstract: MT-III, a brain-specific member of the metallothionein gene family, binds zinc and may facilitate the storage of zinc in neurons. The distribution of MT-III mRNA within the adult brain was determined by solution and in situ hybridization and compared to that of MT-I mRNA. MT-III mRNA is particularly abundant within the cerebral cortex, hippocampus, amygdala, and nuclei at base of the cerebellum. Transgenic mice generated using 11.5 kb of the mouse MT-III 5' flanking region fused to the E. coli lacZ gene express beta-galactosidase in many of the same regions identified by in situ hybridization. MT-III mRNA was present in readily identifiable neurons within the olfactory bulb, hippocampus, and cerebellum, and beta-galactosidase activity was localized to neurons throughout the brain, but not to glia, as determined by costaining with X-Gal and neural- and glia-specific antibodies. There is marked correspondence between the neurons that are rich in MT-III mRNA and those neurons that store zinc in their terminal vesicles. MT-III is found complexed with zinc in vivo and its expression in cultured cells leads to the intracellular accumulation of zinc and enhanced histochemical detection of zinc. These results are discussed in light of the possibility that MT-III may participate in the utilization of zinc as a neuromodulator.
    BibTeX:
    @article{MASTERS1994,
      author = {MASTERS, BA and QUAIFE, CJ and ERICKSON, JC and KELLY, EJ and FROELICK, GJ and ZAMBROWICZ, BP and BRINSTER, RL and PALMITER, RD},
      title = {METALLOTHIONEIN-III IS EXPRESSED IN NEURONS THAT SEQUESTER ZINC IN SYNAPTIC VESICLES},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {10},
      pages = {5844-5857}
    }
    
    MATSUDA, L., BONNER, T. & LOLAIT, S. LOCALIZATION OF CANNABINOID RECEPTOR MESSENGER-RNA IN RAT-BRAIN {1993} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {327}({4}), pp. {535-550} 
    article  
    Abstract: Cannabinoid receptor mRNA was localized in adult rat brain by S-35-tailed oligonucleotide probes and in situ hybridization histochemistry. Labelling is described as uniform or non-uniform depending on the relative intensities of individual cells expressing cannabinoid receptor mRNA within a given region or nucleus. Uniform labelling was found in the hypothalamus, thalamus, basal ganglia, cerebellum and brainstem. Non-uniform labelling that resulted from the presence of cells displaying two easily distinguishable intensities of hybridization signals was observed in several regions and nuclei in the forebrain (cerebral cortex, hippocampus, amygdala, certain olfactory structures). Olfactory-associated structures, basal ganglia, hippocampus, and cerebellar cortex displayed the heaviest amounts of labelling. Many regions that displayed cannabinoid receptor mRNA could reasonably be identified as sources for cannabinoid receptors on the basis of well documented hodologic data. Other sites that were also clearly labelled could not be assigned as logical sources of cannabinoid receptors. The localization of cannabinoid receptor mRNA indicates that sensory, motor, cognitive, limbic, and autonomic systems should all be influenced by the activation of this receptor by either exogenous cannabimimetics, including marijuana, or the yet unknown endogenous `'cannabinoid'' ligand.
    BibTeX:
    @article{MATSUDA1993,
      author = {MATSUDA, LA and BONNER, TI and LOLAIT, SJ},
      title = {LOCALIZATION OF CANNABINOID RECEPTOR MESSENGER-RNA IN RAT-BRAIN},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1993},
      volume = {327},
      number = {4},
      pages = {535-550}
    }
    
    Mayford, M., Bach, M., Huang, Y., Wang, L., Hawkins, R. & Kandel, E. Control of memory formation through regulated expression of a CaMKII transgene {1996} SCIENCE
    Vol. {274}({5293}), pp. {1678-1683} 
    article  
    Abstract: One of the major limitations in the use of genetically modified mice for studying cognitive,, functions is the lack of regional and temporal control of gene function, To overcome these limitations, a forebrain-specific promoter was combined with the tetracycline transactivator system to achieve both regional and temporal control of transgene expression, Expression of an activated calcium-independent form of calcium-calmodulin-dependent dent kinase II (CaMKII) resulted in a loss of hippocampal long-term potentiation in response to 10-hertz stimulation and a deficit in spatial memory, a form of explicit memory, Suppression of transgene expression reversed both the physiological and the memory deficit, When the transgene was expressed at high levels in the lateral amygdala and the striatum but not other forebrain Structures, there was a deficit in fear conditioning, an implicit memory task, that also was reversible Thus, the CaMKII signaling pathway is critical for both explicit and implicit memory storage,in a manner that is independent of its potential role in development.
    BibTeX:
    @article{Mayford1996,
      author = {Mayford, M and Bach, ME and Huang, YY and Wang, L and Hawkins, RD and Kandel, ER},
      title = {Control of memory formation through regulated expression of a CaMKII transgene},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {1996},
      volume = {274},
      number = {5293},
      pages = {1678-1683}
    }
    
    McCarley, R., Wible, C., Frumin, M., Hirayasu, Y., Levitt, J., Fischer, I. & Shenton, M. MRI anatomy of schizophrenia {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({9}), pp. {1099-1119} 
    article  
    Abstract: Structural magnetic resonance imaging (MRI) data have provided much evidence in support of our current view that schizophrenia is a brain disorder with altered brain structure, and consequently involving more than a simple disturbance in neurotransmission. This review surveys 118 peer-reviewed studies with control group from 1987 to May 1998 Most studies (81 do not find abnormalities of whole brain/intracranial contents, while lateral ventricle enlargement is reported in 77 and third ventricle enlargement in 67 The temporal lobe was the brain parenchymal region with the most consistently documented abnormalities. Volume decreases were found in 62% of 37 studies of whole temporal lobe, and in 81% of 16 studies of the superior temporal gyrus (and in 100% with gray matter separately evaluated). Fully 77% of the 30 studies of the medial temporal lobe reported volume reduction in one or more of its constituent structures (hippocampus, amygdala, parahippocampal gyrus). Despite evidence for frontal lobe functional abnormalities, structural MRI investigations less consistently found abnormalities, with 55% describing volume reduction. It may be that frontal lobe volume changes are small, and near the threshold for MRI detection. The parietal and occipital lobes were much less studied; about half of the studies showed positive findings. Most studies of cortical gray matter (86 found volume reductions were not diffuse, but more pronounced in certain areas. About two thirds of the studies of subcortical structures of thalamus, corpus callosum and basal ganglia (which tend to increase volume with typical neuroleptics), show positive findings, as do almost all (91 studies of cavum septi pellucidi (CSP). Most data were consistent with a developmental model, but growing evidence was compatible also with progressive, neurodegenerative features, suggesting a ``two-hit'' model of schizophrenia, for which a cellular hypothesis is discussed. The relationship of clinical symptoms to MRI findings is reviewed, as is the growing evidence suggesting structural abnormalities differ in affective (bipolar) psychosis and schizophrenia. (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{McCarley1999,
      author = {McCarley, RW and Wible, CG and Frumin, M and Hirayasu, Y and Levitt, JJ and Fischer, IA and Shenton, ME},
      title = {MRI anatomy of schizophrenia},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {1999},
      volume = {45},
      number = {9},
      pages = {1099-1119}
    }
    
    McDonald, A. Cortical pathways to the mammalian amygdala {1998} PROGRESS IN NEUROBIOLOGY
    Vol. {55}({3}), pp. {257-332} 
    article  
    Abstract: The amygdaloid nuclear complex is critical for producing appropriate emotional and behavioral responses to biologically relevant sensory stimuli. It constitutes an essential link between sensory and limbic areas of the cerebral cortex and subcortical brain regions, such as the hypothalamus, brainstem, and striatum, that are responsible for eliciting emotional and motivational responses. This review summarizes the anatomy and physiology of the cortical pathways to the amygdala in the rat, cat and monkey. Although the basic anatomy of these systems in the cat and monkey was largely delineated in studies conducted during the 1970s and 1980s, detailed information regarding the cortico-amygdalar pathways in the rat was only obtained in the past several years. The purpose of this review is to describe the results of recent studies in the rat and to compare the organization of cortico-amygdalar projections in this species with that seen in the cat and monkey. In all three species visual, auditory, and somatosensory information is transmitted to the amygdala by a series of modality-specific cortico-cortical pathways (''cascades'') that originate in the primary sensory cortices and flow toward higher order association areas. The cortical areas in the more distal portions of these cascades have stronger and more extensive projections to the amygdala than the more proximal areas. In all three species olfactory and gustatory/visceral information has access to the amygdala at an earlier stage of cortical processing than vis auditory and somatosensory information. There are also important polysensory cortical inputs to the mammalian amygdala from the prefrontal and hippocampal regions. Whereas the overall organization of cortical pathways is basically similar in all mammalian species, there is anatomical evidence which suggests that there are important differences in the extent of convergence of cortical projections in the primate versus the nonprimate amygdala. (C) 1998 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{McDonald1998,
      author = {McDonald, AJ},
      title = {Cortical pathways to the mammalian amygdala},
      journal = {PROGRESS IN NEUROBIOLOGY},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1998},
      volume = {55},
      number = {3},
      pages = {257-332}
    }
    
    MCDONALD, R. & WHITE, N. PARALLEL INFORMATION-PROCESSING IN THE WATER MAZE - EVIDENCE FOR INDEPENDENT MEMORY-SYSTEMS INVOLVING DORSAL STRIATUM AND HIPPOCAMPUS {1994} BEHAVIORAL AND NEURAL BIOLOGY
    Vol. {61}({3}), pp. {260-270} 
    article  
    Abstract: This experiment investigated the ability of rats with dorsal striatal or fornix damage to learn the location of a visible platform in a water maze. We also assessed the animals ability to find the platform when it was hidden (submerged). Rats with neurotoxic damage to the dorsal striatum acquired both the visible and hidden platform versions of the task, but when required to choose between the spatial location they had learned and the visible platform in a new location they swam first to the old spatial location. Rats with radio-frequency damage to the fornix acquired the visible platform version of the water maze task but failed to learn about the platform's location in space. When the visible platform was moved to a new location they swam directly to it. Normal rats acquired both the visible and hidden platform versions of the task. These findings suggest that in the absence of a functional neural system that includes dorsal striatum, spatial information predominantly controlled behavior even in the presence of a cue that the animals had previously been reinforced for approaching; In the absence of a functional hippocampal system behavior was not affected by spatial information and responding to local reinforced cues was enhanced. The results support the idea that different neural substrates in the mammalian nervous system acquire different types of information simultaneously and in parallel. (C) 1994 Academic Press, Inc.
    BibTeX:
    @article{MCDONALD1994,
      author = {MCDONALD, RJ and WHITE, NM},
      title = {PARALLEL INFORMATION-PROCESSING IN THE WATER MAZE - EVIDENCE FOR INDEPENDENT MEMORY-SYSTEMS INVOLVING DORSAL STRIATUM AND HIPPOCAMPUS},
      journal = {BEHAVIORAL AND NEURAL BIOLOGY},
      publisher = {ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS},
      year = {1994},
      volume = {61},
      number = {3},
      pages = {260-270}
    }
    
    MCDONALD, R. & WHITE, N. A TRIPLE DISSOCIATION OF MEMORY-SYSTEMS - HIPPOCAMPUS, AMYGDALA, AND DORSAL STRIATUM {1993} BEHAVIORAL NEUROSCIENCE
    Vol. {107}({1}), pp. {3-22} 
    article  
    Abstract: This study investigated the respective roles of the hippocampus, the amygdala, and the dorsal striatum in learning and memory. A standard set of experimental conditions for studying the effects of lesions to the three brain areas using an 8-arm radial maze was used: a win-shift version, a conditioned cue preference (CCP) version, and a win-stay version. Damage to the hippocampal system impaired acquisition of the win-shift task but not the CCP or win-stay tasks. Damage to the lateral amygdala impaired acquisition of the CCP task but not the win-shift or win-stay tasks. Damage to the dorsal striatum impaired acquisition of the win-stay task but not the win-shift or CCP tasks. These results are consistent with the hypothesis that the mammalian brain may be capable of acquiring different kinds of information with different, more-or-less independent neural systems. A neural system that includes the hippocampus may acquire information about the relationships among stimuli and events. A neural system that includes the amygdala may mediate the rapid acquisition of behaviors based on biologically significant events with affective properties. A neural system that includes the dorsal striatum may mediate the formation of reinforced stimulus-response associations.
    BibTeX:
    @article{MCDONALD1993,
      author = {MCDONALD, RJ and WHITE, NM},
      title = {A TRIPLE DISSOCIATION OF MEMORY-SYSTEMS - HIPPOCAMPUS, AMYGDALA, AND DORSAL STRIATUM},
      journal = {BEHAVIORAL NEUROSCIENCE},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1993},
      volume = {107},
      number = {1},
      pages = {3-22}
    }
    
    McEwen, B. Mood disorders and allostatic load {2003} BIOLOGICAL PSYCHIATRY
    Vol. {54}({3}), pp. {200-207} 
    article DOI  
    Abstract: The brain controls both the physiologic and the behavioral coping responses to daily events as well as major stressors, and the nervous system is itself a target of the mediators of those responses through circulating hormones. The amygdala and hippocampus interpret what is stressful and regulate appropriate responses. The amygdala becomes hyperactive in posttraumatic stress disorder (PTSD) and depressive illness, and hypertrophy of amygdala nerve cells is reported after repeated stress in an animal model. The hippocampus expresses adrenal steroid receptors. It undergoes atrophy in several psychiatric disorders and responds to repeated stressors with decreased dendritic branching and reduction in number of neurons in the dentate gyrus. Stress promotes adaptation (''allostasis''), but a perturbed diurnal rhythm or failed shutoff of mediators after stress (''allostatic state'') leads, over time, to wear and tear on the body (''allostatic load''). Neural changes mirror the pattern seen in the cardiovascular, metabolic, and immune systems, that is, short-term adaptation versus long-term damage. Allostatic load leads to impaired immunity, atherosclerosis, obesity, bone demineralization, and atrophy of nerve cells in brain. Allostatic load is seen in major depressive illness and may also be expressed in other chronic anxiety disorders such as PTSD and should be documented. (C) 2003 Society of Biological Psychiatry.
    BibTeX:
    @article{McEwen2003,
      author = {McEwen, BS},
      title = {Mood disorders and allostatic load},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2003},
      volume = {54},
      number = {3},
      pages = {200-207},
      note = {Conference on Mood Disorders and Medical Illness, WASHINGTON, D.C., NOV 12, 2002},
      doi = {{10.1016/S0006-3223(03)00177-X}}
    }
    
    McEwen, B.S. Physiology and neurobiology of stress and adaptation: Central role of the brain {2007} PHYSIOLOGICAL REVIEWS
    Vol. {87}({3}), pp. {873-904} 
    article DOI  
    Abstract: McEwen BS. Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain. Physiol Rev 87:873-904, 2007; doi:10.1152/physrev.00041.2006.-The brain is the key organ of the response to stress because it determines what is threatening and, therefore, potentially stressful, as well as the physiological and behavioral responses which can be either adaptive or damaging. Stress involves two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Beyond the ``flight-or-fight'' response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body (''allostatic load''). Yet, hormones associated with stress protect the body in the short-run and promote adaptation (''allostasis''). The brain is a target of stress, and the hippocampus was the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. Stress and stress hormones produce both adaptive and maladaptive effects on this brain region throughout the life course. Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience.
    BibTeX:
    @article{McEwen2007,
      author = {McEwen, Bruce S.},
      title = {Physiology and neurobiology of stress and adaptation: Central role of the brain},
      journal = {PHYSIOLOGICAL REVIEWS},
      publisher = {AMER PHYSIOLOGICAL SOC},
      year = {2007},
      volume = {87},
      number = {3},
      pages = {873-904},
      doi = {{10.1152/physrev.00041.2006}}
    }
    
    McGaugh, J. The amygdala modulates the consolidation of memories of emotionally arousing experiences {2004} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {27}, pp. {1-28} 
    article DOI  
    Abstract: Converging findings of animal and human studies provide compelling evidence that the amygdala is critically involved in enabling us to acquire and retain lasting memories of emotional experiences. This review focuses primarily on the findings of research investigating the role of the amygdala in modulating the consolidation of long-term memories. Considerable evidence from animal studies investigating the effects of posttraining systemic or intra-amygdala infusions of hormones and drugs, as well as selective lesions of specific amygdala nuclei, indicates that (a) the amygdala mediates the memory-modulating effects of adrenal stress hormones and several classes of neurotransmitters; (b) the effects are selectively mediated by the basolateral complex of the amygdala (BLA); (c) the influences involve interactions of several neuromodulatory systems within the BLA that converge in influencing noradrenergic and muscarinic cholinergic activation; (d) the BLA modulates memory consolidation via efferents to other brain regions, including the caudate nucleus, nucleus accumbens, and cortex; and (e) the BLA modulates the consolidation of memory of many different kinds of information. The findings of human brain imaging studies are consistent with those of animal studies in suggesting that activation of the amygdala influences the consolidation of long-term memory; the degree of activation of the amygdala by emotional arousal during encoding of emotionally arousing material (either pleasant or unpleasant) correlates highly with subsequent recall. The activation of neuromodulatory systems affecting the BLA and its projections to other brain regions involved in processing different kinds of information plays a key role in enabling emotionally significant experiences to be well remembered.
    BibTeX:
    @article{McGaugh2004,
      author = {McGaugh, JL},
      title = {The amygdala modulates the consolidation of memories of emotionally arousing experiences},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      publisher = {ANNUAL REVIEWS},
      year = {2004},
      volume = {27},
      pages = {1-28},
      doi = {{10.1146/annurev.neuro.27.070203.144157}}
    }
    
    McGaugh, J. Neuroscience - Memory - a century of consolidation {2000} SCIENCE
    Vol. {287}({5451}), pp. {248-251} 
    article  
    Abstract: The memory consolidation hypothesis proposed 100 years ago by Muller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mechanisms. This review examines the progress made over the century in understanding the time-dependent processes that create our lasting memories.
    BibTeX:
    @article{McGaugh2000,
      author = {McGaugh, JL},
      title = {Neuroscience - Memory - a century of consolidation},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {2000},
      volume = {287},
      number = {5451},
      pages = {248-251}
    }
    
    McGaugh, J., Cahill, L. & Roozendaal, B. Involvement of the amygdala in memory storage: Interaction with other brain systems {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({24}), pp. {13508-13514} 
    article  
    Abstract: There is extensive evidence that the amygdala is involved in affectively influenced memory, The central hypothesis guiding the research reviewed in this paper is that emotional arousal activates the amygdala and that such activation results in the modulation of memory storage occurring in other brain regions, Several lines of evidence support this view, First, the effects of stress-related hormones (epinephrine and glucocorticoids) are mediated by influences involving the amygdala, In rats, lesions of the amygdala and the stria terminalis block the effects of posttraining administration of epinephrine and glucocorticoids on memory, Furthermore, memory is enhanced by posttraining intra amygdala infusions of drugs that activate beta-adrenergic and glucocorticoid receptors, Additionally, infusion of beta-adrenergic blockers into the amygdala blocks the memory-modulating effects of epinephrine and glucocorticoids, as well as those of drugs affecting opiate and GABAergic systems, Second, an intact amygdala is not required for expression of retention, Inactivation of the amygdala prior to retention testing (by posttraining lesions or drug infusions) does not block retention performance, Third, findings of studies using human subjects are consistent with those of animal experiments. beta-Blockers and amygdala lesions attenuate the effects of emotional arousal on memory, Additionally, 3-week recall of emotional material is highly correlated with positron-emission tomography activation (cerebral glucose metabolism) of the right amygdala during encoding, These findings provide strong evidence supporting the hypothesis that the amygdala is involved in modulating long-term memory storage.
    BibTeX:
    @article{McGaugh1996,
      author = {McGaugh, JL and Cahill, L and Roozendaal, B},
      title = {Involvement of the amygdala in memory storage: Interaction with other brain systems},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1996},
      volume = {93},
      number = {24},
      pages = {13508-13514},
      note = {Colloquium on Memory - Recording Experience in Cells and Circuits, IRVINE, CA, FEB 17-20, 1996}
    }
    
    McGaugh, J. & Roozendaal, B. Role of adrenal stress hormones in forming lasting memories in the brain {2002} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {12}({2}), pp. {205-210} 
    article  
    Abstract: Recent experiments investigating the effects of adrenal stress hormones on memory provide extensive evidence that epinephrine and glucocorticoids modulate long-term memory consolidation in animals and human subjects. Release of norepinephrine and activation of beta-adrenoceptors within the basolateral amygdala is critical in mediating adrenal stress hormone regulation of memory consolidation.
    BibTeX:
    @article{McGaugh2002,
      author = {McGaugh, JL and Roozendaal, B},
      title = {Role of adrenal stress hormones in forming lasting memories in the brain},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      publisher = {CURRENT BIOLOGY LTD},
      year = {2002},
      volume = {12},
      number = {2},
      pages = {205-210}
    }
    
    McKernan, M. & ShinnickGallagher, P. Fear conditioning induces a lasting potentiation of synaptic currents in vitro {1997} NATURE
    Vol. {390}({6660}), pp. {607-611} 
    article  
    Abstract: The amygdala plays a critical role in the mediation of emotional responses, particularly fear, in both humans and animals(1-4). Fear conditioning, a conditioned learning paradigm, has served as a model for emotional learning in animals, and the neuroanatomical circuitry underlying the auditory fear-conditioning paradigm is well characterized(5). Synaptic transmission in the medial geniculate nucleus (MGN) to lateral nucleus of the amygdala (LA) pathway, a key segment of the auditory fear conditioning circuit, is mediated largely through N-methyl-D-aspartate (NMDA) and non-NMDA (such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)) glutamate receptors(6); the potential for neural plasticity in this pathway is suggested by its capacity to support long-term potentiation (LTP)(7,8). Here we report a long-lasting increase in the synaptic efficacy of the MGN-LA pathway attributable to fear-conditioning itself, rather than an electrically induced model of learning. Fear-conditioned animals show a presynaptic facilitation of AMPA-receptor-mediated transmission, directly measured in vitro with whole-cell recordings in lateral amygdala neurons. These findings represent one of the first in vitro measures of synaptic plasticity resulting from emotional learning by whole animals.
    BibTeX:
    @article{McKernan1997,
      author = {McKernan, MG and ShinnickGallagher, P},
      title = {Fear conditioning induces a lasting potentiation of synaptic currents in vitro},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1997},
      volume = {390},
      number = {6660},
      pages = {607-611}
    }
    
    Mesulam, M. From sensation to cognition {1998} BRAIN
    Vol. {121}({Part 6}), pp. {1013-1052} 
    article  
    Abstract: Sensory information undergoes extensive associative elaboration and attentional modulation as it becomes incorporated into the texture of cognition. This process occurs along a core synaptic hierarchy which includes the primary sensory, upstream unimodal, downstream unimodal, heteromodal, paralimbic and limbic zones of the cerebral cortex. Connections from one zone to another are reciprocal and allow higher synaptic levels to exert a feedback (top-down) influence upon earlier levels of processing. Each cortical area provides a nexus for the convergence of afferents and divergence of efferents. The resultant synaptic organization supports parallel as well as serial processing, and allows each sensory event to initiate multiple cognitive and behavioural outcomes. Upstream sectors of unimodal association areas encode basic features of sensation such as colour, motion, form and pitch. More complex contents of sensory experience such as objects, faces, word-forms, spatial locations and sound sequences become encoded within downstream sectors of unimodal areas by groups of coarsely tuned neurons. The highest synaptic levels of sensory-fugal processing are occupied by heteromodal, paralimbic and limbic cortices, collectively known as transmodal areas. The unique role of these areas is to bind multiple unimodal and other transmodal areas into distributed but integrated multimodal representations. Transmodal areas in the midtemporal cortex, Wernicke's area, the hippocampalentorhinal complex and the posterior parietal cortex provide critical gateways for transforming perception into recognition, word-forms into meaning, scenes and events into experiences, and spatial locations into targets for exploration. All cognitive processes arise from analogous associative transformations of similar sets of sensory inputs. The differences in the resultant cognitive operation are determined by the anatomical and physiological properties of the transmodal node that acts as the critical gateway for the dominant transformation. Interconnected sets of transmodal nodes provide anatomical and computational epicentres for large-scale neurocognitive networks. In keeping with the principles of selectively distributed processing, each epicentre of a large-scale network displays a relative specialization for a specific behavioural component of its principal neurospychological domain. The destruction of transmodal epicentres causes global impairments such as multimodal anemia, neglect and amnesia, whereas their selective disconnection from relevant unimodal areas elicits modality-specific impairments such as prosopagnosia, pure word blindness and category-specific anemias. The human brain contains at least five anatomically distinct networks. The network for spatial awareness is based on transmodal epicentres in the posterior parietal cortex and the frontal eye fields; the language network on epicentres in Wernicke's and Broca's areas; the explicit memory/emotion network on epicentres in the hippocampal-entorhinal complex and the amygdala; the face-object recognition network on epicentres in the midtemporal and temporopolar cortices; and the working memory-executive function network on epicentres in the lateral prefrontal cortex and perhaps the posterior parietal cortex. Individual sensory modalities give rise to streams of processing directed to transmodal nodes belonging to each of these networks. The fidelity of sensory channels is actively protected through approximately four synaptic levels of sensory-fugal processing. The modality-specific cortices at these four synaptic levels encode the most veridical representations of experience. Attentional, motivational and emotional modulations, including those related to working memory, novelty-seeking and mental imagery, become increasingly more pronounced within downstream components of unimodal areas, where they help to create a highly edited subjective version of the world. The prefrontal cortex plays a critical role in these attentional and emotional modulations and allows neural responses to reflect the significance rather than the surface properties of sensory events. Additional modulatory influences are exerted by the cholinergic and monoaminergic pathways of the ascending reticular activating system. Working memory, one of the most prominent manifestations of prefrontal cortex activity, prolongs the neural impact of environmental and mental events in a way that enriches the texture of consciousness. The synaptic architecture of large-scale networks and the manifestations of working memory, novelty-seeking behaviours and mental imagery collectively help to loosen the rigid stimulus-response bonds that dominate the behaviour of lower animal species. This phylogenetic trend has helped to shape the unique properties of human consciousness and to induce the emergence of second-order (symbolic) representations related to language. Through the advent of language and the resultant ability to communicate abstract concepts, the critical pacemaker for human cognitive development has shifted from the extremely slow process of structural brain evolution to the much more rapid one of distributed computations where each individual intelligence can become incorporated into an interactive lattice that promotes the transgenerational transfer and accumulation of knowledge.
    BibTeX:
    @article{Mesulam1998,
      author = {Mesulam, MM},
      title = {From sensation to cognition},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {1998},
      volume = {121},
      number = {Part 6},
      pages = {1013-1052}
    }
    
    MEUNIER, M., BACHEVALIER, J., MISHKIN, M. & MURRAY, E. EFFECTS ON VISUAL RECOGNITION OF COMBINED AND SEPARATE ABLATIONS OF THE ENTORHINAL AND PERIRHINAL CORTEX IN RHESUS-MONKEYS {1993} JOURNAL OF NEUROSCIENCE
    Vol. {13}({12}), pp. {5418-5432} 
    article  
    Abstract: Performance on visual delayed nonmatching-to-sample was assessed in rhesus monkeys with combined and separate ablations of the perirhinal and entorhinal cortex, as well as in unoperated controls. Combined (i.e., rhinal cortex) lesions yielded a striking impairment on this task, one almost as severe as that seen after combined amygdalohippocampal removals that included some of this subjacent cortex (Mishkin, 1978; Murray and Mishkin, 1984). Ablations of the perirhinal cortex alone produced a deficit nearly as severe as that found after rhinal cortex lesions, whereas ablations of the entorhinal cortex alone produced only a mild deficit. Contrary to the conclusion from an earlier study (Murray and Mishkin, 1 986), the present results demonstrate not only that damage limited to the rhinal cortex is sufficient to produce a severe loss in visual recognition, but also that such damage leads to a far greater loss than damage to any other single structure in the medial part of the tem oral lobe.
    BibTeX:
    @article{MEUNIER1993,
      author = {MEUNIER, M and BACHEVALIER, J and MISHKIN, M and MURRAY, EA},
      title = {EFFECTS ON VISUAL RECOGNITION OF COMBINED AND SEPARATE ABLATIONS OF THE ENTORHINAL AND PERIRHINAL CORTEX IN RHESUS-MONKEYS},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1993},
      volume = {13},
      number = {12},
      pages = {5418-5432}
    }
    
    Mezey, E., Toth, Z., Cortright, D., Arzubi, M., Krause, J., Elde, R., Guo, A., Blumberg, P. & Szallasi, A. Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human {2000} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {97}({7}), pp. {3655-3660} 
    article  
    Abstract: The cloned vanilloid receptor VR1 has attracted recent attention as a molecular integrator of painful stimuli on primary sensory neurons. The existence of vanilloid-sensitive neurons in the brain is, however, controversial. In this study, we have used an antibody and a complementary RNA probe to explore the distribution of neurons that express VR1 in rat and in certain areas of human brain. In the rat, we observed VR1-expressing neurons throughout the whole neuroaxis, including all cortical areas (in layers 3 and 5), several members of the limbic system (e.g., hippocampus, central amygdala, and both medial and lateral habenula), striatum, hypothalamus, centromedian and paraventricular thalamic nuclei, substantia nigra, reticular formation, locus coeruleus, cerebellum, and inferior olive. VR1-immunopositive cells also were found in the third and fifth layers of human parietal cortex. Reverse transcription-PCR performed with rat VR1-specific primers verified the expression of VR1 mRNA in cortex, hippocampus, and hypothalamus. In the central nervous system, neonatal capsaicin treatment depleted VR1 mRNA from the spinal nucleus of the trigeminal nerve, but not from other areas such as the inferior olive. The finding that VR1 is expressed not only in primary sensory neurons but also in several brain nuclei is of great importance in that it places VRs in a much broader perspective than pain perception. VRs in the brain (and putative endogenous vanilloids) may be involved in the control of emotions, learning, and satiety, just to name a few exciting possibilities.
    BibTeX:
    @article{Mezey2000,
      author = {Mezey, E and Toth, ZE and Cortright, DN and Arzubi, MK and Krause, JE and Elde, R and Guo, A and Blumberg, PM and Szallasi, A},
      title = {Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {2000},
      volume = {97},
      number = {7},
      pages = {3655-3660}
    }
    
    Milad, M. & Quirk, G. Neurons in medial prefrontal cortex signal memory for fear extinction {2002} NATURE
    Vol. {420}({6911}), pp. {70-74} 
    article DOI  
    Abstract: Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov(1) it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction(2,3), indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.
    BibTeX:
    @article{Milad2002,
      author = {Milad, MR and Quirk, GJ},
      title = {Neurons in medial prefrontal cortex signal memory for fear extinction},
      journal = {NATURE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2002},
      volume = {420},
      number = {6911},
      pages = {70-74},
      doi = {{10.1038/nature01138}}
    }
    
    Mirenowicz, J. & Schultz, W. Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli {1996} NATURE
    Vol. {379}({6564}), pp. {449-451} 
    article  
    Abstract: MIDBRAIN dopamine systems are crucially involved in motivational processes underlying the learning and execution of goal-directed behaviour(1-5). Dopamine neurons in monkeys are uniformly activated by unpredicted appetitive stimuli such as food and liquid rewards and conditioned, reward-predicting stimuli. By contrast, fully predicted stimuli are ineffective(6-8), and the omission of predicted reward depresses their activity(9). These characteristics follow associative-learning rules(10,11), suggesting that dopamine responses report an error in reward prediction(12). Accordingly, neural network models are efficiently trained using a dopamine-like reinforcement signal(13,14). However, it is unknown whether the responses to environmental stimuli concern specific motivational attributes or reflect more general stimulus salience(4,15). To resolve this, we have compared dopamine impulse responses to motivationally opposing appetitive and aversive stimuli. In contrast to appetitive events, primary and conditioned non-noxious aversive stimuli either failed to activate dopamine neurons or, in cases of close resemblance with appetitive stimuli, induced weaker responses than appetitive stimuli. Thus, dopamine neurons preferentially report environmental stimuli with appetitive rather than aversive motivational value.
    BibTeX:
    @article{Mirenowicz1996,
      author = {Mirenowicz, J and Schultz, W},
      title = {Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1996},
      volume = {379},
      number = {6564},
      pages = {449-451}
    }
    
    MISERENDINO, M., SANANES, C., MELIA, K. & DAVIS, M. BLOCKING OF ACQUISITION BUT NOT EXPRESSION OF CONDITIONED FEAR-POTENTIATED STARTLE BY NMDA ANTAGONISTS IN THE AMYGDALA {1990} NATURE
    Vol. {345}({6277}), pp. {716-718} 
    article  
    BibTeX:
    @article{MISERENDINO1990,
      author = {MISERENDINO, MJD and SANANES, CB and MELIA, KR and DAVIS, M},
      title = {BLOCKING OF ACQUISITION BUT NOT EXPRESSION OF CONDITIONED FEAR-POTENTIATED STARTLE BY NMDA ANTAGONISTS IN THE AMYGDALA},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1990},
      volume = {345},
      number = {6277},
      pages = {716-718}
    }
    
    MISHKIN, M. MEMORY IN MONKEYS SEVERELY IMPAIRED BY COMBINED BUT NOT BY SEPARATE REMOVAL OF AMYGDALA AND HIPPOCAMPUS {1978} NATURE
    Vol. {273}({5660}), pp. {297-298} 
    article  
    BibTeX:
    @article{MISHKIN1978,
      author = {MISHKIN, M},
      title = {MEMORY IN MONKEYS SEVERELY IMPAIRED BY COMBINED BUT NOT BY SEPARATE REMOVAL OF AMYGDALA AND HIPPOCAMPUS},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1978},
      volume = {273},
      number = {5660},
      pages = {297-298}
    }
    
    Mitra, S., Hoskin, E., Yudkovitz, J., Pear, L., Wilkinson, H., Hayashi, S., Pfaff, D., Ogawa, S., Rohrer, S., Schaeffer, J., McEwen, B. & Alves, S. Immunolocalization of estrogen receptor beta in the mouse brain: Comparison with estrogen receptor alpha {2003} ENDOCRINOLOGY
    Vol. {144}({5}), pp. {2055-2067} 
    article DOI  
    Abstract: Estrogen receptor alpha (ERalpha) and ERalpha are members of the steroid nuclear receptor family that modulate gene transcription in an estrogen-dependent manner. ER mRNA and protein have been detected both peripherally and in the central nervous system, with most data having come from the rat. Here we report the development of an ERbeta-selective antibody that cross-reacts with mouse, rat, and human ERbeta protein and its use to determine the distribution of ERbeta in the murine brain. Further, a previously characterized polyclonal antibody to ERalpha was used to compare the distribution of the two receptors in the first comprehensive description of ER distribution specifically in the mouse brain. ERbeta immunoreactivity (ir) was primarily localized to cell nuclei within select regions of the brain, including the olfactory bulb, cerebral cortex, septum, preoptic area, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamic nucleus, thalamus, ventral tegmental area, substantia nigra, dorsal raphe, locus coeruleus, and cerebellum. Extranuclear-ir was detected in several areas, including fibers of the olfactory bulb, CA3 stratum lucidum, and CA1 stratum radiatum of the hippocampus and cerebellum. Although both receptors were generally expressed in a similar distribution through the brain, nuclear ERalpha-ir was the predominant subtype in the hippocampus, preoptic area, and most of the hypothalamus, whereas it was sparse or absent from the cerebral cortex and cerebellum. Collectively, these findings demonstrate the region-selective expression of ERbeta and ERalpha in the adult ovariectomized mouse brain. These data provide an anatomical framework for understanding the mechanisms by which estrogen regulates specific neural systems in the mouse.
    BibTeX:
    @article{Mitra2003,
      author = {Mitra, SW and Hoskin, E and Yudkovitz, J and Pear, L and Wilkinson, HA and Hayashi, S and Pfaff, DW and Ogawa, S and Rohrer, SP and Schaeffer, JM and McEwen, BS and Alves, SE},
      title = {Immunolocalization of estrogen receptor beta in the mouse brain: Comparison with estrogen receptor alpha},
      journal = {ENDOCRINOLOGY},
      publisher = {ENDOCRINE SOC},
      year = {2003},
      volume = {144},
      number = {5},
      pages = {2055-2067},
      doi = {{10.1210/en.2002-221069}}
    }
    
    MOGA, M. & GRAY, T. EVIDENCE FOR CORTICOTROPIN-RELEASING FACTOR, NEUROTENSIN, AND SOMATOSTATIN IN THE NEURAL PATHWAY FROM THE CENTRAL NUCLEUS OF THE AMYGDALA TO THE PARABRACHIAL NUCLEUS {1985} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {241}({3}), pp. {275-284} 
    article  
    BibTeX:
    @article{MOGA1985,
      author = {MOGA, MM and GRAY, TS},
      title = {EVIDENCE FOR CORTICOTROPIN-RELEASING FACTOR, NEUROTENSIN, AND SOMATOSTATIN IN THE NEURAL PATHWAY FROM THE CENTRAL NUCLEUS OF THE AMYGDALA TO THE PARABRACHIAL NUCLEUS},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1985},
      volume = {241},
      number = {3},
      pages = {275-284}
    }
    
    MOGA, M., WEIS, R. & MOORE, R. EFFERENT PROJECTIONS OF THE PARAVENTRICULAR THALAMIC NUCLEUS IN THE RAT {1995} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {359}({2}), pp. {221-238} 
    article  
    Abstract: The paraventricular nucleus of the thalamus (PVT) receives input from all major components of the circadian timing system, including the suprachiasmatic nucleus (SCN), the intergeniculate leaflet and the retina. For a better understanding of the role of this nucleus in circadian timing, we examined the distribution of its efferent projections using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The efferent projections of the PVT are loosely organized along its dorsal-ventral and anterior-posterior axes. The anterior PVT sends projections to the SCN; the dorsomedial and ventromedial hypothalamic nuclei; the lateral septum; the bed nucleus of the stria terminalis; the central and basomedial amygdaloid nuclei; the anterior olfactory nucleus; the olfactory tubercle; the nucleus accumbens; the infralimbic, piriform, and perirhinal cortices; the ventral subiculum; and the endopiriform nucleus. A small PHA-L injection, restricted to the ventral portion of the anterior PVT, produces a similar pattern of labeling, except for a marked decrease in the number of labeled fibers in the hypothalamus, cortex, and lateral septum and an increase in labeling in the endopiriform nucleus and basolateral amygdaloid nucleus. The posterior PVT has a more limited efferent distribution than the anterior PVT, terminating in the anterior olfactory nucleus; the olfactory tubercle; the nucleus accumbens; and the central, basolateral, and basomedial nuclei of the amygdala. Our results show that the anterior PVT is ideally situated to relay circadian timing information from the SCN to brain areas involved in visceral and motivational aspects of behavior and to provide feedback regulation of the SCN. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{MOGA1995,
      author = {MOGA, MM and WEIS, RP and MOORE, RY},
      title = {EFFERENT PROJECTIONS OF THE PARAVENTRICULAR THALAMIC NUCLEUS IN THE RAT},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1995},
      volume = {359},
      number = {2},
      pages = {221-238}
    }
    
    MOLLEREAU, C., PARMENTIER, M., MAILLEUX, P., BUTOUR, J., MOISAND, C., CHALON, P., CAPUT, D., VASSART, G. & MEUNIER, J. ORL1, A NOVEL MEMBER OF THE OPIOID RECEPTOR FAMILY - CLONING, FUNCTIONAL EXPRESSION AND LOCALIZATION {1994} FEBS LETTERS
    Vol. {341}({1}), pp. {33-38} 
    article  
    Abstract: Selective PCR amplification of human and mouse genomic DNAs with oligonucleotides encoding highly conserved regions of the delta-opioid and somatostatin receptors generated a human DNA probe (hOP01, 761 bp) and its murine counterpart (mOP86, 447 bp). hOP01 was used to screen a cDNA library from human brainstem. A clone (named hORL1) was isolated, sequenced and found to encode a protein of 370 amino acids whose primary structure displays the seven putative membrane-spanning domains of a G protein-coupled membrane receptor. The hORL1 receptor is most closely related to opioid receptors not only on structural (sequence) but also on functional grounds: hORL1 is 49-50% identical to the murine mu-, delta- and kappa-opioid receptors and, in CHO-K1 cells stably transfected with a pRc/CMV:hORL1 construct, ORL1 mediates inhibition of adenylyl cyclase by etorphine, a `universal' (nonselective) opiate agonist. Yet, hORL1 appears not to be a typical opioid receptor. Neither is it a somatostatin or delta (N-allylnormetazocine) receptor. mRNAs hybridizing with synthetic oligonucleotides complementary to mOP86 are present in many regions of the mouse brain and spinal cord, particularly in limbic (amygdala, hippocampus, septum, habenula,...) and hypothalamic structures. We conclude that the hORL1 receptor is a new member of the opioid receptor family with a potential role in modulating a number of brain functions, including instinctive behaviours and emotions.
    BibTeX:
    @article{MOLLEREAU1994,
      author = {MOLLEREAU, C and PARMENTIER, M and MAILLEUX, P and BUTOUR, JL and MOISAND, C and CHALON, P and CAPUT, D and VASSART, G and MEUNIER, JC},
      title = {ORL1, A NOVEL MEMBER OF THE OPIOID RECEPTOR FAMILY - CLONING, FUNCTIONAL EXPRESSION AND LOCALIZATION},
      journal = {FEBS LETTERS},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1994},
      volume = {341},
      number = {1},
      pages = {33-38}
    }
    
    MORECRAFT, R., GEULA, C. & MESULAM, M. CYTOARCHITECTURE AND NEURAL AFFERENTS OF ORBITOFRONTAL CORTEX IN THE BRAIN OF THE MONKEY {1992} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {323}({3}), pp. {341-358} 
    article  
    Abstract: The orbitofrontal cortex of the monkey can be subdivided into a caudal agranular sector, a transitional dysgranular sector, and an anterior granular sector. The neural input into these sectors was investigated with the help of large horseradish peroxidase injections that covered the different sectors of orbitofrontal cortex. The distribution of retrograde labeling showed that the majority of the cortical projections to orbitofrontal cortex arises from a restricted set of telencephalic sources, which include prefrontal cortex, lateral, and inferomedial temporal cortex, the temporal pole, cingulate gyrus, insula, entorhinal cortex, hippocampus, amygdala, and claustrum. The posterior portion of the orbitofrontal cortex receives additional input from the piriform cortex and the anterolateral portion from gustatory, somatosensory, and premotor areas. Thalamic projections to the orbitofrontal cortex arise from midline and intralaminar nuclei, from the anteromedial nucleus, the medial dorsal nucleus, and the pulvinar nucleus. Orbitofrontal cortex also receives projections from the hypothalamus, nucleus basalis, ventral tegmental area, the raphe nuclei, the nucleus locus coeruleus, and scattered neurons of the pontomesencephalic tegmentum. The non-isocortical (agranular-dysgranular) sectors of orbitofrontal cortex receive more intense projections from the non-isocortical sectors of paralimbic areas, the hippocampus, amygdala, and midline thalamic nuclei, whereas the isocortical (granular) sector receives more intense projections from the dorsolateral prefrontal area, the granular insula, granular temporopolar cortex, posterolateral temporal cortex, and from the medial dorsal and pulvinar thalamic nuclei. Retrograde labeling within cingulate, entorhinal, and hippocampal cortices was most pronounced when the injection site extended medially into the dysgranular paraolfactory cortex of the gyrus rectus, an area that can be conceptualized as an orbitofrontal extension of the cingulate complex. These observations demonstrate that the orbitofrontal cortex has cytoarchitectonically organized projections and that it provides a convergence zone for afferents from heteromodal association and limbic areas. The diverse connections of orbitofrontal cortex are in keeping with the participation of this region in visceral, gustatory, and olfactory functions and with its importance in memory, motivation, and epileptogenesis.
    BibTeX:
    @article{MORECRAFT1992,
      author = {MORECRAFT, RJ and GEULA, C and MESULAM, MM},
      title = {CYTOARCHITECTURE AND NEURAL AFFERENTS OF ORBITOFRONTAL CORTEX IN THE BRAIN OF THE MONKEY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1992},
      volume = {323},
      number = {3},
      pages = {341-358}
    }
    
    MORGAN, M. & LEDOUX, J. DIFFERENTIAL CONTRIBUTION OF DORSAL AND VENTRAL MEDIAL PREFRONTAL CORTEX TO THE ACQUISITION AND EXTINCTION OF CONDITIONED FEAR IN RATS {1995} BEHAVIORAL NEUROSCIENCE
    Vol. {109}({4}), pp. {681-688} 
    article  
    Abstract: The emotional reactivity of rats with lesions of the dorsal portion of medial prefrontal cortex (mPFC) was examined using a classical fear conditioning paradigm. Conditioned fear behavior (freezing responses) was measured during both the acquisition and extinction phases of the task. Lesions enhanced fear reactivity to both the conditioned stimlulus (CS) and contextual stimuli during both phases, suggesting that dorsal mPFC lesions produce a general increase in fear reactivity in response to fear conditioning. M. A. Morgan, L. M. Romanski, and J. E. LeDoux (1993) found that lesions just ventral to the present lesions had no effect during acquisition of the same task and prolonged the fear response to the CS (but not the context) during extinction. Thus, both dorsal and ventral regions of mPFC are involved in the fear system, but each modulates different aspects of fear responsivity.
    BibTeX:
    @article{MORGAN1995,
      author = {MORGAN, MA and LEDOUX, JE},
      title = {DIFFERENTIAL CONTRIBUTION OF DORSAL AND VENTRAL MEDIAL PREFRONTAL CORTEX TO THE ACQUISITION AND EXTINCTION OF CONDITIONED FEAR IN RATS},
      journal = {BEHAVIORAL NEUROSCIENCE},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1995},
      volume = {109},
      number = {4},
      pages = {681-688}
    }
    
    MORGAN, M., ROMANSKI, L. & LEDOUX, J. EXTINCTION OF EMOTIONAL LEARNING - CONTRIBUTION OF MEDIAL PREFRONTAL CORTEX {1993} NEUROSCIENCE LETTERS
    Vol. {163}({1}), pp. {109-113} 
    article  
    Abstract: Stimuli associated with painful or otherwise unpleasant events acquire aversive emotional properties in animals and humans. Subsequent presentation of the stimulus alone (in the absence of the unpleasant event) leads to the eventual extinction of the aversive reaction. Although the neural basis of emotional learning has been studied extensively, considerably less is known about the neural basis of emotional extinction. In the present study, we show that the medial prefrontal cortex plays an important role in the regulation of fear extinction in rats, a finding that may help elucidate the mechanisms and, possibly, the treatment of disorders of uncontrolled fear, such as anxiety, phobic, panic and posttraumatic stress disorders in humans.
    BibTeX:
    @article{MORGAN1993,
      author = {MORGAN, MA and ROMANSKI, LM and LEDOUX, JE},
      title = {EXTINCTION OF EMOTIONAL LEARNING - CONTRIBUTION OF MEDIAL PREFRONTAL CORTEX},
      journal = {NEUROSCIENCE LETTERS},
      publisher = {ELSEVIER SCI IRELAND LTD},
      year = {1993},
      volume = {163},
      number = {1},
      pages = {109-113}
    }
    
    Morris, J., Friston, K., Buchel, C., Frith, C., Young, A., Calder, A. & Dolan, R. A neuromodulatory role for the human amygdala in processing emotional facial expressions {1998} BRAIN
    Vol. {121}({Part 1}), pp. {47-57} 
    article  
    Abstract: Localized amygdalar lesions in humans produce deficits in the recognition of fearful facial expressions. We used functional neuroimaging to test two hypotheses: (i) that the amygdala and some of its functionally connected structures mediate specific neural responses to fearful expressions; (ii) that the early visual processing of emotional faces can be influenced by amygdalar activity. Normal subjects were scanned using PET while they performed a gender discrimination task involving static grey-scale images of faces expressing varying degrees of fear or happiness. In support of the first hypothesis, enhanced activity in the left amygdala, left pulvinar, left anterior insula and bilateral anterior cingulate gyri was observed during the processing of fearful faces. Evidence consistent with the second hypothesis was obtained by a demonstration that amygdalar responses predict expression specific neural activity in extrastriate cortex.
    BibTeX:
    @article{Morris1998a,
      author = {Morris, JS and Friston, KJ and Buchel, C and Frith, CD and Young, AW and Calder, AJ and Dolan, RJ},
      title = {A neuromodulatory role for the human amygdala in processing emotional facial expressions},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {1998},
      volume = {121},
      number = {Part 1},
      pages = {47-57}
    }
    
    Morris, J., Frith, C., Perrett, D., Rowland, D., Young, A., Calder, A. & Dolan, R. A differential neural response in the human amygdala to fearful and happy facial expressions {1996} NATURE
    Vol. {383}({6603}), pp. {812-815} 
    article  
    Abstract: THE amygdala is thought to play a crucial role in emotional and social behaviour(1). Animal studies implicate the amygdala in both fear conditioning(2) and face perception(3). In humans, lesions of the amygdala can lead to selective deficits in the recognition of fearful facial expressions(4,5) and impaired fear conditioning(6,7), and direct electrical stimulation evokes fearful emotional responses(8). Here we report direct in vivo evidence of a differential neural response in the human amygdala to facial expressions of fear and happiness, Positron-emission tomography (PET) measures of neural activity were acquired while subjects viewed photographs of fearful or happy faces, varying systematically in emotional intensity, The neuronal response in the left amygdala was significantly greater to fearful as opposed to happy expressions, Furthermore, this response showed a significant interaction with the intensity of emotion (increasing with increasing fearfulness, decreasing with increasing happiness). The findings provide direct evidence that the human amygdala is engaged in processing the emotional salience of faces, with a specificity of response to fearful facial expressions.
    BibTeX:
    @article{Morris1996,
      author = {Morris, JS and Frith, CD and Perrett, DI and Rowland, D and Young, AW and Calder, AJ and Dolan, RJ},
      title = {A differential neural response in the human amygdala to fearful and happy facial expressions},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1996},
      volume = {383},
      number = {6603},
      pages = {812-815}
    }
    
    Morris, J., Ohman, A. & Dolan, R. A subcortical pathway to the right amygdala mediating ``unseen'' fear {1999} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {96}({4}), pp. {1680-1685} 
    article  
    Abstract: Neuroimaging studies have shown, differential amygdala responses to masked (''unseen'') emotional stimuli. How visual signals related to such unseen stimuli access the amygdala is unknown. A possible pathway, involving the superior colliculus and pulvinar, is suggested by observations of patients with striate cortex lesions who show preserved abilities to localize and discriminate visual stimuli that are not consciously perceived (''blindsight''). We used measures of right amygdala neural activity acquired from volunteer subjects viewing masked fear-conditioned faces to determine whether a colliculo-pulvinar pathway was engaged during processing of these unseen target stimuli, Increased connectivity between right amygdala, pulvinar, and superior colliculus was evident when fear-conditioned faces were unseen rather than seen. Right amygdala connectivity with fusiform and orbitofrontal cortices decreased in the same condition, By contrast, the left amygdala, whose activity did not discriminate seen and unseen fear-conditioned targets, showed no masking-dependent changes in connectivity with superior colliculus or pulvinar. These results suggest that a subcortical pathway to the right amygdala, via midbrain and thalamus, provides a route for processing behaviorally relevant unseen visual events in parallel to a cortical route necessary for conscious identification.
    BibTeX:
    @article{Morris1999,
      author = {Morris, JS and Ohman, A and Dolan, RJ},
      title = {A subcortical pathway to the right amygdala mediating ``unseen'' fear},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1999},
      volume = {96},
      number = {4},
      pages = {1680-1685}
    }
    
    Morris, J., Ohman, A. & Dolan, R. Conscious and unconscious emotional learning in the human amygdala {1998} NATURE
    Vol. {393}({6684}), pp. {467-470} 
    article  
    Abstract: If subjects are shown an angry face as a target visual stimulus for less than forty milliseconds and are then immediately shown an expressionless mask, these subjects report seeing the mask but not the target. However, an aversively conditioned masked target can elicit an emotional response from subjects without being consciously perceived(1,2). Here we study the mechanism of this unconsciously mediated emotional learning. We measured neural activity in volunteer subjects who were presented with two angry faces, one of which, through previous classical conditioning, was associated with a burst of white noise. In half of the trials, the subjects' awareness of the angry faces was prevented by backward masking with a neutral face. A significant neural response was elicited in the right, but not left, amygdala to masked presentations of the conditioned angry face. Unmasked presentations of the same face produced enhanced neural activity in the left, but not right, amygdala. Our results indicate that, first, the human amygdala can discriminate between stimuli solely on the basis of their acquired behavioural significance, and second, this response is lateralized according to the subjects' level of awareness of the stimuli.
    BibTeX:
    @article{Morris1998,
      author = {Morris, JS and Ohman, A and Dolan, RJ},
      title = {Conscious and unconscious emotional learning in the human amygdala},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1998},
      volume = {393},
      number = {6684},
      pages = {467-470}
    }
    
    Morrison, R., Wenzel, H., Kinoshita, Y., Robbins, C., Donehower, L. & Schwartzkroin, P. Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death {1996} JOURNAL OF NEUROSCIENCE
    Vol. {16}({4}), pp. {1337-1345} 
    article  
    Abstract: The tumor suppressor gene p53 recently has been associated with the induction of cell death in response to some forms of cellular damage. A possible role for p53-related modulation of neuronal viability has been suggested by the finding that p53 expression is increased in damaged neurons in models of ischemia and epilepsy. We evaluated the possibility that p53 expression (in knockout mice) is required for induction of cell damage in a model of seizure activity normally associated with well defined patterns of cell loss. Subcutaneous injection of kainic acid, a potent excitotoxin, induced comparable seizures in both wild-type mice (+/+) and mice deficient in p53 (-/-). Using a silver impregnation technique to examine neurodegeneration in animals killed 7 d after kainate injection, we found that a majority of +/+ mice exhibited extensive cell loss in the hippocampus, involving subregions CA1, CA3, the hilus, and the subiculum. Apoptotic cell death, as identified with an in situ nick end labeling technique to detect DNA fragmentation, was confirmed in CA1- but not CA3-degenerating neurons. In marked contrast, a majority of p53 -/- mice displayed no signs of cell damage; in the remaining p53 -/- mice, damage was mild to moderate and was confined almost entirely to cells in CA3b of the dorsal hippocampus. In +/+ mice, but not in -/- mice, damaged neurons also were observed in the amygdala, piriform cortex, cerebral cortex, caudate-putamen, and thalamus after kainate treatment. The pattern and extent of damage in mice heterozygous for p53 (+/-) were identical to those seen in +/+ mice, suggesting that a single copy of p53 is sufficient to confer neuronal vulnerability. These results demonstrate that p53 influences viability in multiple neuronal subtypes and brain regions after excitotoxic insult.
    BibTeX:
    @article{Morrison1996,
      author = {Morrison, RS and Wenzel, HJ and Kinoshita, Y and Robbins, CA and Donehower, LA and Schwartzkroin, PA},
      title = {Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1996},
      volume = {16},
      number = {4},
      pages = {1337-1345}
    }
    
    Muda, M., Boschert, U., Dickinson, R., Martinou, J., Martinou, I., Camps, M., Schlegel, W. & Arkinstall, S. MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase {1996} JOURNAL OF BIOLOGICAL CHEMISTRY
    Vol. {271}({8}), pp. {4319-4326} 
    article  
    Abstract: MKP-1 (also known as CL100, 3CH134, Erp, and hVH-1) exemplifies a class of dual-specificity phosphatase able to reverse the activation of mitogen-activated protein (MAP) kinase family members by dephosphorylating critical tyrosine and threonine residues. We now report the cloning of MKP-3, a novel protein phosphatase that also suppresses MAP kinase activation state. The deduced amino acid sequence of MKP-3 is 36% identical to MKP-1 and contains the characteristic extended active-site sequence motif VXVHCXXGXSRSXTXXXAYLM (where X is any amino acid) as well as two N-terminal CH2 domains displaying homology to the cell cycle regulator Cdc25 phosphatase. When expressed in COS-7 cells, MKP-3 blocks both the phosphorylation and enzymatic activation of ERK2 by mitogens. Northern analysis reveals a single mRNA species of 2.7 kilobases with an expression pattern distinct from other dual-specificity phosphatases. MKP-3 is expressed in lung, heart, brain, and kidney, but not significantly in skeletal muscle or testis. In situ hybridization studies of MKP-3 in brain reveal enrichment within the CA1, CA3, and CA4 layers of the hippocampus. Metrazole-stimulated seizure activity triggers rapid (<1 h) but transient up-regulation of MKP-3 mRNA in the cortex, piriform cortex, and some amygdala nuclei. Metrazole stimulated similar regional up-regulation of MKP-1, although this was additionally induced within the thalamus. MKP-3 mRNA also undergoes powerful induction in PC12 cells after 3 h of nerve growth factor treatment. This response appears specific insofar as epidermal growth factor and dibutyryl cyclic AMP fail to induce significant MKP-3 expression. Subcellular localization of epitope-tagged MKP-3 in sympathetic neurons reveals expression in the cytosol with exclusion from the nucleus. Together, these observations indicate that MKP-3 is a novel dual-specificity phosphatase that displays a distinct tissue distribution, subcellular localization, and regulated expression, suggesting a unique function in controlling MAP kinase family members. Identification of a second partial cDNA clone (MKP-X) encoding the C-terminal 280 amino acids of an additional phosphatase that is 76% identical to MKP-3 suggests the existence of a distinct structurally homologous subfamily of MAP kinase phosphatases.
    BibTeX:
    @article{Muda1996,
      author = {Muda, M and Boschert, U and Dickinson, R and Martinou, JC and Martinou, I and Camps, M and Schlegel, W and Arkinstall, S},
      title = {MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase},
      journal = {JOURNAL OF BIOLOGICAL CHEMISTRY},
      publisher = {AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC},
      year = {1996},
      volume = {271},
      number = {8},
      pages = {4319-4326}
    }
    
    Murray, E. & Mishkin, M. Object recognition and location memory in monkeys with excitotoxic lesions of the amygdala and hippocampus {1998} JOURNAL OF NEUROSCIENCE
    Vol. {18}({16}), pp. {6568-6582} 
    article  
    Abstract: Earlier work indicated that combined but not separate removal of the amygdala and hippocampus, together with the cortex underlying these structures, leads to a severe impairment in visual recognition. More recent work, however, has shown that removal of the rhinal cortex, a region subjacent to the amygdala and rostral hippocampus, yields nearly the same impairment as the original removal. This raises the possibility that the earlier results were attributable to combined damage to the rostral and caudal portions of the rhinal cortex rather than to the combined amygdala and hippocampal removal. To test this possibility, we trained rhesus monkeys on delayed nonmatching-to-sample, a measure of visual recognition, gave them selective lesions of the amygdala and hippocampus made with the excitotoxin ibotenic acid, and then assessed their recognition abilities by using increasingly longer delays and list lengths, including delays as long as 40 min, Postoperatively, monkeys with the combined amygdala and hippocampal lesions performed as well as intact controls at every stage of testing, The same monkeys also were unimpaired relative to controls on an analogous test of spatial memory, delayed nonmatching-to-location. It is unlikely that unintended sparing of target structures can account for the lack of impairment; there was a significant positive correlation between the percentage of damage to the hippocampus and scores on portions of the recognition performance test, suggesting that, paradoxically, the greater the hippocampal damage, the better the recognition. The results show that, within the medial temporal lobe, the rhinal cortex is both necessary and sufficient for visual recognition.
    BibTeX:
    @article{Murray1998,
      author = {Murray, EA and Mishkin, M},
      title = {Object recognition and location memory in monkeys with excitotoxic lesions of the amygdala and hippocampus},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1998},
      volume = {18},
      number = {16},
      pages = {6568-6582}
    }
    
    NABEKURA, J., OOMURA, Y., MINAMI, T., MIZUNO, Y. & FUKUDA, A. MECHANISM OF THE RAPID EFFECT OF 17-BETA-ESTRADIOL ON MEDIAL AMYGDALA NEURONS {1986} SCIENCE
    Vol. {233}({4760}), pp. {226-228} 
    article  
    BibTeX:
    @article{NABEKURA1986,
      author = {NABEKURA, J and OOMURA, Y and MINAMI, T and MIZUNO, Y and FUKUDA, A},
      title = {MECHANISM OF THE RAPID EFFECT OF 17-BETA-ESTRADIOL ON MEDIAL AMYGDALA NEURONS},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {1986},
      volume = {233},
      number = {4760},
      pages = {226-228}
    }
    
    NACHMAN, M. & ASHE, J. EFFECTS OF BASOLATERAL AMYGDALA LESIONS ON NEOPHOBIA, LEARNED TASTE AVERSIONS, AND SODIUM APPETITE IN RATS {1974} JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
    Vol. {87}({4}), pp. {622-643} 
    article  
    BibTeX:
    @article{NACHMAN1974,
      author = {NACHMAN, M and ASHE, JH},
      title = {EFFECTS OF BASOLATERAL AMYGDALA LESIONS ON NEOPHOBIA, LEARNED TASTE AVERSIONS, AND SODIUM APPETITE IN RATS},
      journal = {JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1974},
      volume = {87},
      number = {4},
      pages = {622-643}
    }
    
    Nader, K. Memory traces unbound {2003} TRENDS IN NEUROSCIENCES
    Vol. {26}({2}), pp. {65-72} 
    article  
    Abstract: The idea that new memories are initially `labile' and sensitive to disruption before becoming permanently stored in the wiring of the brain has been dogma for >100 years. Recently, we have revisited the hypothesis that reactivation of a consolidated memory can return it to a labile, sensitive state - in which it can be modified, strengthened, changed or even erased! The data generated from some of the best-described paradigms in memory research, in conjunction with powerful neurobiological technologies, have provided striking support for a very dynamic neuro-biological basis of memory, which is beginning to overturn the old dogma.
    BibTeX:
    @article{Nader2003,
      author = {Nader, K},
      title = {Memory traces unbound},
      journal = {TRENDS IN NEUROSCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {2003},
      volume = {26},
      number = {2},
      pages = {65-72}
    }
    
    Nader, K., Schafe, G. & Le Doux, J. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval {2000} NATURE
    Vol. {406}({6797}), pp. {722-726} 
    article  
    Abstract: `New' memories are initially labile and sensitive to disruption before being consolidated into stable long-term memories(1-5). Much evidence indicates that this consolidation involves the synthesis of new proteins in neurons(6-9). The lateral and basal nuclei of the amygdala (LBA) are believed to be a site of memory storage in fear learning(10). Infusion of the protein synthesis inhibitor anisomycin into the LBA shortly after training prevents consolidation of fear memories(11). Here we show that consolidated fear memories, when reactivated during retrieval, return to a labile state in which infusion of anisomycin shortly after memory reactivation produces amnesia on later tests, regardless of whether reactivation was performed 1 or 14 days after conditioning. The same treatment with anisomycin, in the absence of memory reactivation, left memory intact. Consistent with a time-limited role for protein synthesis production in consolidation, delay of the infusion until six hours after memory reactivation produced no amnesia. Our data show that consolidated fear memories, when reactivated, return to a labile state that requires de novo protein synthesis for reconsolidation. These findings are not predicted by traditional theories of memory consolidation.
    BibTeX:
    @article{Nader2000,
      author = {Nader, K and Schafe, GE and Le Doux, JE},
      title = {Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval},
      journal = {NATURE},
      publisher = {MACMILLAN PUBLISHERS LTD},
      year = {2000},
      volume = {406},
      number = {6797},
      pages = {722-726}
    }
    
    Nambu, T., Sakurai, T., Mizukami, K., Hosoya, Y., Yanagisawa, M. & Goto, K. Distribution of orexin neurons in the adult rat brain {1999} BRAIN RESEARCH
    Vol. {827}({1-2}), pp. {243-260} 
    article  
    Abstract: Orexin (ORX)-A and -B are recently identified neuropeptides, which are specifically localized in neurons within and around the lateral hypothalamic area (LHA) and dorsomedial hypothalamic nucleus (DMH), the regions classically implicated in feeding behavior. Here, we report a further study of the distribution of ORX-containing neurons in the adult rat brain to provide a general overview of the ORX neuronal system. Immunohistochemical study using anti-ORX antiserum showed ORX-immunoreactive (ir) neurons specifically localized within the hypothalamus, including the perifornical nucleus, LHA, DMH, and posterior hypothalamic area. ORX-ir axons and their varicose terminals showed a widespread distribution throughout the adult rat brain. ORX-ir nerve terminals were observed throughout the hypothalamus, including the arcuate nucleus and paraventricular hypothalamic nucleus, regions implicated in the regulation of feeding behavior. We also observed strong staining of ORX-ir varicose terminals in areas outside the hypothalamus, including the cerebral cortex, medial groups of the thalamus, circumventricular organs (subfornical organ and area postrema), Limbic system (hippocampus, amygdala, and indusium griseum), and brain stem (locus coeruleus and raphe nuclei). These results indicate that the ORX system provides a link between the hypothalamus and other brain regions, and that ORX-containing LHA and DMH neurons play important roles in integrating the complex physiology underlying feeding behavior. (C) 1999 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Nambu1999,
      author = {Nambu, T and Sakurai, T and Mizukami, K and Hosoya, Y and Yanagisawa, M and Goto, K},
      title = {Distribution of orexin neurons in the adult rat brain},
      journal = {BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1999},
      volume = {827},
      number = {1-2},
      pages = {243-260}
    }
    
    Neal, C., Mansour, A., Reinscheid, R., Nothacker, H., Civelli, O. & Watson, S. Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat {1999} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {406}({4}), pp. {503-547} 
    article  
    Abstract: Orphanin FQ (OFQ) is the endogenous agonist of the opioid receptor-like receptor (ORL-1). It and its precursor, prepro-OFQ, exhibit structural features suggestive of the opioid peptides. A cDNA encoding the OFQ precursor sequence in the rat recently has been cloned, and the authors recently generated a polyclonal antibody directed against the OFQ peptide. In the present study, the authors used in situ hybridization and immunohistochemistry to examine the distribution of OFQ peptide and mRNA in the central nervous system of the adult rat. OFQ immunoreactivity and prepro-OFQ mRNA expression correlated virtually in all brain areas studied. In the forebrain, OFQ peptide and mRNA were prominent in the neocortex endopiriform nucleus, claustrum, lateral septum, ventral forebrain, hypothalamus, mammillary bodies, central and medial nuclei of the amygdala, hippocampal formation, paratenial and reticular nuclei of the thalamus, medial habenula, and zona incerta. No OFQ was observed in the pineal or pituitary glands. In the brainstem, OFQ was prominent in the ventral tegmental area, substantia nigra, nucleus of the posterior commissure, central gray, nucleus of Darkschewitsch, peripeduncular nucleus, interpeduncular nucleus, tegmental nuclei, locus coeruleus, raphe complex, lateral parabrachial nucleus, inferior olivary complex, vestibular nuclear complex, prepositus hypoglossus, solitary nucleus, nucleus ambiguous, caudal spinal trigeminal nucleus, and reticular formation. In the spinal cord, OFQ was observed throughout the dorsal and ventral horns. The wide distribution of this peptide provides support for its role in a multitude of functions, including not only nociception but also motor and balance control, special sensory processing, and various autonomic and physiologic processes. J. Comp. Neurol. 406:503-547, 1999. (C) 1999 Wiley-Liss, Inc.
    BibTeX:
    @article{Neal1999,
      author = {Neal, CR and Mansour, A and Reinscheid, R and Nothacker, HP and Civelli, O and Watson, SJ},
      title = {Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1999},
      volume = {406},
      number = {4},
      pages = {503-547}
    }
    
    Nelson, M., Saykin, A., Flashman, L. & Riordan, H. Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging - A meta-analytic study {1998} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {55}({5}), pp. {433-440} 
    article  
    Abstract: Background: Although many quantitative magnetic resonance imaging studies have found significant volume reductions in the hippocampi of patients with schizophrenia compared with those of normal control subjects, others have not. Therefore, the issue of hippocampal volume differences associated with schizophrenia remains in question. Methods: Two meta-analyses were conducted to reduce the potential effects of sampling error and methodological differences in data acquisition and analysis. Eighteen studies with a total patient number of 522 and a to tal control number of 426 met the initial selection criteria. Results: Meta-analysis 1 yielded mean effect sizes of 0.37 (P<.001) for the left hippocampus and 0.39 (P<.001) for the right, corresponding to a bilateral reduction of 4 Meta-analysis 2 indicated that the inclusion of the amygdala in the region of interest significantly increased effect sizes across studies (effect size for the left hippocampus and amygdala, 0.67; for the right, 0.72), whereas variables such as illness duration, total slice width, magnet strength, the use of the intracranial volume as a covariate, measurement reliability, and study quality did not. No laterality differences were observed in these data. Conclusions: Schizophrenia is associated with a bilateral volumetric reduction of the hippocampus and probably of the amygdala as well. These findings reinforce the importance of the medial temporal region in schizophrenia and are consistent with frequently reported memory deficits in these patients. Future quantitative magnetic resonance imaging studies evaluating the hippocampal volume should measure the hippocampus and amygdala separately and compare the volumetric reduction in these structures to that observed in other gray matter areas.
    BibTeX:
    @article{Nelson1998,
      author = {Nelson, MD and Saykin, AJ and Flashman, LA and Riordan, HJ},
      title = {Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging - A meta-analytic study},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      publisher = {AMER MEDICAL ASSOC},
      year = {1998},
      volume = {55},
      number = {5},
      pages = {433-440}
    }
    
    Nestler, E., Barrot, M., DiLeone, R., Eisch, A., Gold, S. & Monteggia, L. Neurobiology of depression {2002} NEURON
    Vol. {34}({1}), pp. {13-25} 
    article  
    Abstract: Current treatments for depression are inadequate for many individuals, and progress in understanding the neurobiology of depression is slow. Several promising hypotheses of depression and antidepressant action have been formulated recently. These hypotheses are based largely on dysregulation of the hypothalamic-pituitary-adrenal axis and hippocampus and implicate corticotropin-releasing factor, glucocorticoids, brain-derived neurotrophic factor, and CREB. Recent work has looked beyond hippocampus to other brain areas that are also likely involved. For example, nucleus accumbens, amygdala, and certain hypothalamic nuclei are critical in regulating motivation, eating, sleeping, energy level, circadian rhythm, and responses to rewarding and aversive stimuli, which are all abnormal in depressed patients. A neurobiologic understanding of depression also requires identification of the genes that make individuals vulnerable or resistant to the syndrome. These advances will fundamentally improve the treatment and prevention of depression.
    BibTeX:
    @article{Nestler2002,
      author = {Nestler, EJ and Barrot, M and DiLeone, RJ and Eisch, AJ and Gold, SJ and Monteggia, LM},
      title = {Neurobiology of depression},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2002},
      volume = {34},
      number = {1},
      pages = {13-25}
    }
    
    NORGREN, R. TASTE PATHWAYS TO HYPOTHALAMUS AND AMYGDALA {1976} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {166}({1}), pp. {17-30} 
    article  
    BibTeX:
    @article{NORGREN1976,
      author = {NORGREN, R},
      title = {TASTE PATHWAYS TO HYPOTHALAMUS AND AMYGDALA},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1976},
      volume = {166},
      number = {1},
      pages = {17-30}
    }
    
    O'Doherty, J. Reward representations and reward-related learning in the human brain: insights from neuroimaging {2004} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {14}({6}), pp. {769-776} 
    article DOI  
    Abstract: This review outlines recent findings from human neuroimaging concerning the role of a highly interconnected network of brain areas including orbital and medial prefrontal cortex, amygdala, striatum and dopaminergic mid-brain in reward processing. Distinct reward-related functions can be attributed to different components of this network. Orbitofrontal cortex is involved in coding stimulus reward value and in concert with the amygdala and ventral striatum is implicated in representing predicted future reward. Such representations can be used to guide action selection for reward, a process that depends, at least in part, on orbital and medial prefrontal cortex as well as dorsal striatum.
    BibTeX:
    @article{O'Doherty2004,
      author = {O'Doherty, JP},
      title = {Reward representations and reward-related learning in the human brain: insights from neuroimaging},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      publisher = {CURRENT BIOLOGY LTD},
      year = {2004},
      volume = {14},
      number = {6},
      pages = {769-776},
      doi = {{10.1016/j.conb.2004.10.016}}
    }
    
    O'Doherty, J., Deichmann, R., Critchley, H. & Dolan, R. Neural responses during anticipation of a primary taste reward {2002} NEURON
    Vol. {33}({5}), pp. {815-826} 
    article  
    Abstract: The aim of this study was to determine the brain regions involved in anticipation of a primary taste reward and to compare these regions to those responding to the receipt of a taste reward. Using fMRI, we scanned human subjects who were presented with visual cues that signaled subsequent reinforcement with a pleasant sweet taste (1 M glucose), a moderately unpleasant salt taste (0.2 M saline), or a neutral taste. Expectation of a pleasant taste produced activation in dopaminergic midbrain, posterior dorsal amygdala, striatum, and orbitofrontal cortex (OFC). Apart from OFC, these regions were not activated by reward receipt. The findings indicate that when rewards are predictable, brain regions recruited during expectation are, in part, dissociable from areas responding to reward receipt.
    BibTeX:
    @article{O'Doherty2002,
      author = {O'Doherty, JP and Deichmann, R and Critchley, HD and Dolan, RJ},
      title = {Neural responses during anticipation of a primary taste reward},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2002},
      volume = {33},
      number = {5},
      pages = {815-826}
    }
    
    O'Doherty, J., Rolls, E., Francis, S., Bowtell, R. & McGlone, F. Representation of pleasant and aversive taste in the human brain {2001} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {85}({3}), pp. {1315-1321} 
    article  
    Abstract: In this study, the representation of taste in the orbitofrontal cortex was investigated to determine whether or not a pleasant and an aversive taste have distinct or overlapping representations in this region. The pleasant stimulus used was sweet taste (1 M glucose), and the unpleasant stimulus was salt taste (0.1 M NaCl). We used an ON/OFF block design in a 3T fMRI scanner with a tasteless solution delivered in the OFF period to control for somatosensory or swallowing-related effects. It was found that parts of the orbitofrontal cortex were activated (P < 0.005 corrected) by glucose (in 6/7 subjects) and by salt (in 6/7 subjects). In the group analysis, separate areas of the orbitofrontal cortex were found to be activated by pleasant and aversive tastes. The involvement of the amygdala in the representation of pleasant as well as aversive tastes was also investigated. The amygdala was activated (region of interest analysis, P < 0.025 corrected) by the pleasant taste of glucose (5/7 subjects) as well as by the aversive taste of salt (4/7 subjects). Activation by both stimuli was also found in the frontal opercular/insular (primary) taste cortex. We conclude that the orbitofrontal cortex is involved in processing tastes that have both positive and negative affective valence and that different areas of the orbitofrontal cortex may be activated by pleasant and unpleasant tastes. We also conclude that the amygdala is activated not only by an affectively unpleasant taste, but also by a taste that is affectively pleasant, thus providing evidence that the amygdala is involved in effects produced by positively affective as well as by negatively affective stimuli.
    BibTeX:
    @article{O'Doherty2001,
      author = {O'Doherty, J and Rolls, ET and Francis, S and Bowtell, R and McGlone, F},
      title = {Representation of pleasant and aversive taste in the human brain},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      publisher = {AMER PHYSIOLOGICAL SOC},
      year = {2001},
      volume = {85},
      number = {3},
      pages = {1315-1321}
    }
    
    Ochsner, K., Bunge, S., Gross, J. & Gabrieli, J. Rethinking feelings: An fMRI study of the cognitive regulation of emotion {2002} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {14}({8}), pp. {1215-1229} 
    article  
    Abstract: The ability to cognitively regulate emotional responses to aversive events is important for mental and physical health. Little is known, however, about neural bases of the cognitive control of emotion. The present study employed functional magnetic resonance imaging to examine the neural systems used to reappraise highly negative scenes in unemotional terms. Reappraisal of highly negative scenes reduced subjective experience of negative affect. Neural correlates of reappraisal were increased activation of the lateral and medial prefrontal regions and decreased activation of the amygdala and medial orbito-frontal cortex. These findings support the hypothesis that prefrontal cortex is involved in constructing reappraisal strategies that can modulate activity in multiple emotion-processing systems.
    BibTeX:
    @article{Ochsner2002,
      author = {Ochsner, KN and Bunge, SA and Gross, JJ and Gabrieli, JDE},
      title = {Rethinking feelings: An fMRI study of the cognitive regulation of emotion},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      publisher = {M I T PRESS},
      year = {2002},
      volume = {14},
      number = {8},
      pages = {1215-1229}
    }
    
    Ochsner, K. & Gross, J. The cognitive control of emotion {2005} TRENDS IN COGNITIVE SCIENCES
    Vol. {9}({5}), pp. {242-249} 
    article DOI  
    Abstract: The capacity to control emotion is important for human adaptation. Questions about the neural bases of emotion regulation have recently taken on new importance, as functional imaging studies in humans have permitted direct investigation of control strategies that draw upon higher cognitive processes difficult to study in nonhumans. Such studies have examined (1) controlling attention to, and (2) cognitively changing the meaning of, emotionally evocative stimuli. These two forms of emotion regulation depend upon interactions between prefrontal and cingulate control systems and cortical and subcortical emotion-generative systems. Taken together, the results suggest a functional architecture for the cognitive control of emotion that dovetails with findings from other human and nonhuman research on emotion.
    BibTeX:
    @article{Ochsner2005,
      author = {Ochsner, KN and Gross, JJ},
      title = {The cognitive control of emotion},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      publisher = {ELSEVIER SCIENCE LONDON},
      year = {2005},
      volume = {9},
      number = {5},
      pages = {242-249},
      doi = {{10.1016/j.tics.2005.03.010}}
    }
    
    Ochsner, K., Ray, R., Cooper, J., Robertson, E., Chopra, S., Gabrieli, J. & Gross, J. For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion {2004} NEUROIMAGE
    Vol. {23}({2}), pp. {483-499} 
    article DOI  
    Abstract: Functional neuroimaging studies examining the neural bases of the cognitive control of emotion have found increased prefrontal and decreased amygdala activation for the reduction or down-regulation of negative emotion. It is unknown, however, (1) whether the same neural systems underlie the enhancement or tip-regulation of emotion, and (2) whether altering the nature of the regulatory strategy alters the neural systems mediating the regulation. To address these questions using functional magnetic resonance imaging (fMRI), participants up- and down-regulated negative emotion either by focusing internally on the self-relevance of aversive scenes or by focusing externally on alternative meanings for pictured actions and their situational contexts Results indicated (1a) that both up- and down-regulating negative emotion recruited prefrontal and anterior cingulate regions implicated in cognitive control, (1b) that amygdala activation was modulated up or down in accord with the regulatory goal, and (1c) that up-regulation uniquely recruited regions of left rostromedial PFC implicated in the retrieval of emotion knowledge, whereas down-regulation uniquely recruited regions of right lateral and orbital PFC implicated in behavioral inhibition. Results also indicated that (2) self-focused regulation recruited medial prefrontal regions implicated in internally focused processing, whereas situation-focused regulation recruited lateral prefrontal regions implicated in externally focused processing. These data suggest that both common and distinct neural systems support various forms of reappraisal and that which particular prefrontal systems modulate the amygdala in different ways depends on the regulatory goal and strategy employed. (C) 2004 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Ochsner2004,
      author = {Ochsner, KN and Ray, RD and Cooper, JC and Robertson, ER and Chopra, S and Gabrieli, JDE and Gross, JJ},
      title = {For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion},
      journal = {NEUROIMAGE},
      publisher = {ACADEMIC PRESS INC ELSEVIER SCIENCE},
      year = {2004},
      volume = {23},
      number = {2},
      pages = {483-499},
      doi = {{10.1016/j.neuroimage.2004.06.030}}
    }
    
    ODONNELL, P. & GRACE, A. SYNAPTIC-INTERACTIONS AMONG EXCITATORY AFFERENTS TO NUCLEUS-ACCUMBENS NEURONS - HIPPOCAMPAL GATING OF PREFRONTAL CORTICAL INPUT {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({5, Part 1}), pp. {3622-3639} 
    article  
    Abstract: The interactions among excitatory inputs arising from the prefrontal cortex, amygdala, and hippocampus, and innervating nucleus accumbens neurons were studied using in vivo intracellular recording techniques. Neurons recorded in the accumbens displayed one of three activity states: (1) silent, (2) spontaneously firing at low, constant rates, or (3) a bistable membrane potential, characterized by alternating periods of activity and silence occurring in concert with spontaneous transitions between two steady-state membrane potentials (average, -77.3 +/- 7.1 mV base, -63.0 +/- 7.4 mV plateau). These neurons also exhibited a high degree of convergence of responses elicited by stimulation of each of the three excitatory inputs tested. Activation of hippocampal afferents, but not cortical, amygdaloid, or thalamic afferents, induced bistable cells to switch to the depolarized (active) state. In contrast, no bistable cells were encountered in the nucleus accumbens following an acute transection of the fornix. Furthermore, microinjection of lidocaine in the vicinity of the hippocampal afferents at the level of the fornix caused a reversible elimination of the plateau phase in bistable cells. These data suggest that hippocampal input is necessary for accumbens neurons to enter a depolarized, active state, Furthermore, activation of prefrontal cortical inputs fail to evoke spike firing in accumbens neurons unless they are in this active state. Consequently, the hippocampus appears to be capable of gating prefrontal corticoaccumbens throughput.
    BibTeX:
    @article{ODONNELL1995,
      author = {ODONNELL, P and GRACE, AA},
      title = {SYNAPTIC-INTERACTIONS AMONG EXCITATORY AFFERENTS TO NUCLEUS-ACCUMBENS NEURONS - HIPPOCAMPAL GATING OF PREFRONTAL CORTICAL INPUT},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1995},
      volume = {15},
      number = {5, Part 1},
      pages = {3622-3639}
    }
    
    Ohman, A., Lundqvist, D. & Esteves, F. The face in the crowd revisited: A threat advantage with schematic stimuli {2001} JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY
    Vol. {80}({3}), pp. {381-396} 
    article DOI  
    Abstract: Schematic threatening, friendly, and neutral faces were used to test the hypothesis that humans preferentially orient their attention toward threat. Using a visual search paradigm, participants searched for discrepant faces in matrices of otherwise identical faces. Across 5 experiments, results consistently showed faster and more accurate detection of threatening than friendly targets. The threat advantage was obvious regardless of whether the conditions favored parallel or serial search (i.e., involved neutral or emotional distractors), and it was valid for inverted faces. Threatening angry faces were more quickly and accurately detected than were other negative faces (sad or ``scheming''), which suggests that the threat advantage can be attributed to threat rather than to the negative valence or the uniqueness of the target display.
    BibTeX:
    @article{Ohman2001a,
      author = {Ohman, A and Lundqvist, D and Esteves, F},
      title = {The face in the crowd revisited: A threat advantage with schematic stimuli},
      journal = {JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {2001},
      volume = {80},
      number = {3},
      pages = {381-396},
      doi = {{10.1037//0022-3514.80.3.381}}
    }
    
    Ohman, A. & Mineka, S. Fears, phobias, and preparedness: Toward an evolved module of fear and fear learning {2001} PSYCHOLOGICAL REVIEW
    Vol. {108}({3}), pp. {483-522} 
    article DOI  
    Abstract: An evolved module for fear elicitation and fear learning with 4 characteristics is proposed. (a) The fear module is preferentially activated in aversive contexts by stimuli that are fear relevant in an evolutionary perspective. (b) Its activation to such stimuli is automatic. (c) It is relatively impenetrable to cognitive control. (d) It originates in a dedicated neural circuitry, centered on the amygdala. Evidence supporting these propositions is reviewed from conditioning studies, both in humans and in monkeys; illusory correlation studies; studies using unreportable stimuli; and studies from animal neuroscience. The fear module is assumed to mediate an emotional level of fear learning that is relatively independent and dissociable from cognitive learning of stimulus relationships.
    BibTeX:
    @article{Ohman2001,
      author = {Ohman, A and Mineka, S},
      title = {Fears, phobias, and preparedness: Toward an evolved module of fear and fear learning},
      journal = {PSYCHOLOGICAL REVIEW},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {2001},
      volume = {108},
      number = {3},
      pages = {483-522},
      doi = {{10.1037//0033-295X.108.3.483}}
    }
    
    OTTERSEN, O. CONNECTIONS OF THE AMYGDALA OF THE RAT .4. CORTICO-AMYGDALOID AND INTRA-AMYGDALOID CONNECTIONS AS STUDIED WITH AXONAL-TRANSPORT OF HORSERADISH-PEROXIDASE {1982} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {205}({1}), pp. {30-48} 
    article  
    BibTeX:
    @article{OTTERSEN1982,
      author = {OTTERSEN, OP},
      title = {CONNECTIONS OF THE AMYGDALA OF THE RAT .4. CORTICO-AMYGDALOID AND INTRA-AMYGDALOID CONNECTIONS AS STUDIED WITH AXONAL-TRANSPORT OF HORSERADISH-PEROXIDASE},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1982},
      volume = {205},
      number = {1},
      pages = {30-48}
    }
    
    PACAK, K., PALKOVITS, M., KOPIN, I. & GOLDSTEIN, D. STRESS-INDUCED NOREPINEPHRINE RELEASE IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS AND PITUITARY-ADRENOCORTICAL AND SYMPATHOADRENAL ACTIVITY - IN-VIVO MICRODIALYSIS STUDIES {1995} FRONTIERS IN NEUROENDOCRINOLOGY
    Vol. {16}({2}), pp. {89-150} 
    article  
    Abstract: The hypothalamic-pituitary-adrenocortical (HPA) axis and the autonomic nervous system are major effector systems that serve to maintain homeostasis during exposure to stressors. In the past decade, interest in neurochemical regulation and in pathways controlling activation of the HPA axis has focused on catecholamines, which are present in high concentrations in specific brain areas-especially in the hypothalamus. The work described in this review has concentrated on the application of in vivo microdialysis in rat brain regions such as the paraventricular nucleus (PVN) of the hypothalamus, the central nucleus of the amygdala (ACE), the bed nucleus of the stria terminalis (BNST), and the posterolateral hypothalamus in order to examine aspects of catecholaminergic function and relationships between altered catecholaminergic function and the HPA axis and sympathoadrenal system activation in stress. Exposure of animals to immobilization (IMMO) markedly and rapidly increases rates of synthesis, release, and metabolism of norepinephrine (NE) in all the brain areas mentioned above and supports previous suggestions that in the PVN NE stimulates release of corticotropin-releasing hormone (CRH). The role of NE in the ACE and the BNST and most other areas possessing noradrenergic innervation remains unclear. Studies involving lower brainstem hemisections show that noradrenergic terminals in the PVN are derived mainly from medullary catecholaminergic groups rather than from the locus ceruleus, which is the main source of NE in the brain. Moreover, the medullary catecholaminergic groups contribute substantially to IMMO-induced noradrenergic activation in the PVN. Data obtained from adrenalectomized rats, with or without glucocorticoid replacement, and from hypercortisolemic rats suggest that glucocorticoids feedback to inhibit CRH release in the PVN, via attenuation of noradrenergic activation. Results from rats exposed to different stressors have indicated substantial differences among stressors in eliciting PVN noradrenergic responses as well as of responses of the HPA, sympathoneural, and adrenomedullary systems. Finally, involvement of other areas that participate in the regulation of the HPA axis such as the ACE, the BNST, and the hippocampus and the importance of stress-induced changes in expression of immediate early genes such as c-fos are discussed.
    BibTeX:
    @article{PACAK1995,
      author = {PACAK, K and PALKOVITS, M and KOPIN, IJ and GOLDSTEIN, DS},
      title = {STRESS-INDUCED NOREPINEPHRINE RELEASE IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS AND PITUITARY-ADRENOCORTICAL AND SYMPATHOADRENAL ACTIVITY - IN-VIVO MICRODIALYSIS STUDIES},
      journal = {FRONTIERS IN NEUROENDOCRINOLOGY},
      publisher = {ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS},
      year = {1995},
      volume = {16},
      number = {2},
      pages = {89-150}
    }
    
    PACKARD, M., CAHILL, L. & MCGAUGH, J. AMYGDALA MODULATION OF HIPPOCAMPAL-DEPENDENT AND CAUDATE NUCLEUS-DEPENDENT MEMORY PROCESSES {1994} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {91}({18}), pp. {8477-8481} 
    article  
    Abstract: These experiments investigated the effects, on memory, of injections of d-amphetamine (10 mu g/0.5 mu l) administered into the amygdala, hippocampus, or caudate nucleus immediately after training in cued or spatial water-maze tasks. In experiment 1, rats received an eight-trial training session on one of the two tasks followed by injections of d-amphetamine or saline. Retention was tested 24 hr later. On the spatial task, intrahippocampal, but not intracaudate, injections of d-amphetamine facilitated retention. In contrast, on the cued task intracaudate, but not intrahippocampal, injections of d-amphetamine facilitated retention. Posttraining intraamygdala injections of d-amphetamine enhanced retention of both tasks. In experiment 2, lidocaine (2% solution; 1.0 mu l) injected intraamygdally prior to the retention test did not block the memory enhancement induced by posttraining intraamygdala injections of d-amphetamine. The findings (i) provide further evidence of a dissociation between the roles of the hippocampus and caudate nucleus in different forms of memory, (ii) indicate that the modulatory role of the amygdala is not limited to either of the two different forms of memory represented in spatial and cued discriminations in a water maze, and (iii) are consistent with previous findings indicating that amygdala influences on memory storage are not mediated by lasting neural changes located within the amygdala.
    BibTeX:
    @article{PACKARD1994,
      author = {PACKARD, MG and CAHILL, L and MCGAUGH, JL},
      title = {AMYGDALA MODULATION OF HIPPOCAMPAL-DEPENDENT AND CAUDATE NUCLEUS-DEPENDENT MEMORY PROCESSES},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1994},
      volume = {91},
      number = {18},
      pages = {8477-8481}
    }
    
    Packard, M. & McGaugh, J. Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning {1996} NEUROBIOLOGY OF LEARNING AND MEMORY
    Vol. {65}({1}), pp. {65-72} 
    article  
    Abstract: Involvement of the hippocampus and caudate nucleus in place and response learning was examined by functionally inactivating these brain regions bilaterally with infusions of lidocaine. Rats were trained to approach a consistently baited arm in a cross-maze from the same start box (four trials/day/14 total days). On Days 8 and 16 a single probe trial was given, in which rats were placed in the start box opposite that used in training and allowed to approach a maze arm. Three minutes prior to the probe trial, rats received bilateral injections of either saline or a 2% lidocaine solution (in order to produce neural inactivation) into either the dorsal hippocampus or dorsolateral caudate nucleus. On the probe trials, rats which entered the baited maze arm (i.e., approached the place where food was located during training) were designated place learners, and rats which entered the unbaited maze arm (i.e., made the same turning response as during training) were designated response learners. Saline-treated rats displayed place learning on the Day 8 probe trial and response learning on the Day 16 probe trial, indicating that with extended training there is a shift in learning mechanisms controlling behavior. Rats given lidocaine injections into the hippocampus showed no preference for place or response learning on the Day 8 probe trial, but displayed response learning on the Day 16 probe trial, indicating a blockade of place learning following inactivation of the hippocampus. Rats given lidocaine injections into the caudate nucleus displayed place learning on both the Day 8 and the Day 16 probe trials, indicating a blockade of response learning following inactivation of the caudate nucleus. The findings indicate: (1) the hippocampus and caudate nucleus selectively mediate expression of place and response learning, respectively (2), in a visually cued extramaze environment, hippocampal-dependent place learning is acquired faster than caudate-dependent response learning, and (3) when animals shift to caudate-dependent response learning with extended training, the hippocampal-based place representation remains intact. (C) 1996 Academic Press, Inc.
    BibTeX:
    @article{Packard1996,
      author = {Packard, MG and McGaugh, JL},
      title = {Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning},
      journal = {NEUROBIOLOGY OF LEARNING AND MEMORY},
      publisher = {ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS},
      year = {1996},
      volume = {65},
      number = {1},
      pages = {65-72}
    }
    
    PACKARD, M. & MCGAUGH, J. DOUBLE DISSOCIATION OF FORNIX AND CAUDATE-NUCLEUS LESIONS ON ACQUISITION OF 2 WATER MAZE TASKS - FURTHER EVIDENCE FOR MULTIPLE MEMORY-SYSTEMS {1992} BEHAVIORAL NEUROSCIENCE
    Vol. {106}({3}), pp. {439-446} 
    article  
    Abstract: The present study examined the effect of lesions of the caudate nucleus or fimbria-fornix on the acquisition of two water maze tasks. In both tasks, two rubber balls with different visual patterns were used as platforms (i.e., cues). The ``correct'' cue was attached to a submerged rectangular platform and could be mounted by an animal to escape the water. The ``incorrect'' cue was attached to a thin round pedestal and could not be mounted. In a spatial version of the task, the correct cue was located in the same quadrant of the maze on all trials, whereas the visual pattern on the cue was varied from trial to trial. Lesions of the fornix, but not the caudate nucleus, impaired acquisition of this spatial task in relation to control animals. In a simultaneous visual discrimination version of the task, the correct cue on all trials was one with a specific visual pattern, and the spatial location of the correct cue was varied from trial to trial. Lesions of the caudate nucleus, but not the fornix, impaired acquisition of this visual discrimination task in relation to control animals. The double dissociation observed supports the hypothesis that the hippocampus and caudate nucleus are parts of systems that differ in the type of memory they mediate.
    BibTeX:
    @article{PACKARD1992,
      author = {PACKARD, MG and MCGAUGH, JL},
      title = {DOUBLE DISSOCIATION OF FORNIX AND CAUDATE-NUCLEUS LESIONS ON ACQUISITION OF 2 WATER MAZE TASKS - FURTHER EVIDENCE FOR MULTIPLE MEMORY-SYSTEMS},
      journal = {BEHAVIORAL NEUROSCIENCE},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1992},
      volume = {106},
      number = {3},
      pages = {439-446}
    }
    
    Pare, D., Quirk, G. & Ledoux, J. New vistas on amygdala networks in conditioned fear {2004} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {92}({1}), pp. {1-9} 
    article DOI  
    Abstract: It is currently believed that the acquisition of classically conditioned fear involves potentiation of conditioned thalamic inputs in the lateral amygdala ( LA). In turn, LA cells would excite more neurons in the central nucleus ( CE) that, via their projections to the brain stem and hypothalamus, evoke fear responses. However, LA neurons do not directly contact brain stem-projecting CE neurons. This is problematic because CE projections to the periaqueductal gray and pontine reticular formation are believed to generate conditioned freezing and fear-potentiated startle, respectively. Moreover, like LA, CE may receive direct thalamic inputs communicating information about the conditioned and unconditioned stimuli. Finally, recent evidence suggests that the CE itself may be a critical site of plasticity. This review attempts to reconcile the current model with these observations. We suggest that potentiated LA outputs disinhibit CE projection neurons via GABAergic intercalated neurons, thereby permitting associative plasticity in CE. Thus plasticity in both LA and CE would be necessary for acquisition of conditioned fear. This revised model also accounts for inhibition of conditioned fear after extinction.
    BibTeX:
    @article{Pare2004,
      author = {Pare, D and Quirk, GJ and Ledoux, JE},
      title = {New vistas on amygdala networks in conditioned fear},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      publisher = {AMER PHYSIOLOGICAL SOC},
      year = {2004},
      volume = {92},
      number = {1},
      pages = {1-9},
      doi = {{10.1152/jn.00153.2004}}
    }
    
    Parkinson, J., Olmstead, M., Burns, L., Robbins, T. & Everitt, B. Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive Pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by D-Amphetamine {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({6}), pp. {2401-2411} 
    article  
    Abstract: Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotor-stimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 mu g) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired during the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotor-stimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.
    BibTeX:
    @article{Parkinson1999,
      author = {Parkinson, JA and Olmstead, MC and Burns, LH and Robbins, TW and Everitt, BJ},
      title = {Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive Pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by D-Amphetamine},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {6},
      pages = {2401-2411}
    }
    
    PATRICK, C. EMOTION AND PSYCHOPATHY - STARTLING NEW INSIGHTS {1994} PSYCHOPHYSIOLOGY
    Vol. {31}({4}), pp. {319-330} 
    article  
    Abstract: Abnormal affective response in psychopaths is conceptualized within a broad theory of emotion that emphasizes reciprocal appetitive and defensive motivational systems. The startle response is proposed as a specific measure of the directional component of emotional activation. I review the literature that indicates that criminal psychopaths do not show the expected potentiation of the startle reflex that normally occurs during processing of aversive stimuli such as unpleasant photographs or punishment cues. Evidence is presented to demonstrate that this deviant response pattern is specific to individuals who display the classic affective symptoms of psychopathy. The core emotional deviation in psychopathy could be a deficit in fear response, which is defined as a failure of aversive cues to prime normal defensive actions. This emotional deficit may represent an extreme variant of normal temperament.
    BibTeX:
    @article{PATRICK1994,
      author = {PATRICK, CJ},
      title = {EMOTION AND PSYCHOPATHY - STARTLING NEW INSIGHTS},
      journal = {PSYCHOPHYSIOLOGY},
      publisher = {SOC PSYCHOPHYSIOL RES},
      year = {1994},
      volume = {31},
      number = {4},
      pages = {319-330},
      note = {33rd Annual Meeting of the Society-for-Psychophysiological-Research, ROTTACH-EGERN, GERMANY, OCT, 1993}
    }
    
    Perez-Reyes, E., Cribbs, L., Daud, A., Lacerda, A., Barclay, J., Williamson, M., Fox, M., Rees, M. & Lee, J. Molecular characterization of a neuronal low-voltage-activated T-type calcium channel {1998} NATURE
    Vol. {391}({6670}), pp. {896-900} 
    article  
    Abstract: The molecular diversity of voltage-activated calcium channels was established by studies showing that channels could be distinguished by their voltage-dependence, deactivation and single-channel conductance(1-3). Low-voltage-activated channels are called `T' type because their currents are both transient (owing. to fast inactivation) and tiny (owing to small conductance)(2). T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing(4). Here we report the identification of a neuronal T-type channel. Our cloning strategy began with an analysis of Genbank sequences defined as sharing homology with calcium channels. We sequenced an expressed sequence tag (EST), then used it to done a full-length complementary DNA from rat brain. Northern blot analysis indicated that this gene is expressed predominantly in brain, in particular the amygdala, cerebellum and thalamus. We mapped the human gene to chromosome 17q22, and the mouse gene to chromosome 11. Functional expression of the channel was measured in Xenopus oocytes. Based on the channel's distinctive voltage dependence, slow deactivation kinetics, and 7.5-pS single-channel conductance, we conclude that this channel is a low-voltage-activated T-type calcium channel.
    BibTeX:
    @article{Perez-Reyes1998,
      author = {Perez-Reyes, E and Cribbs, LL and Daud, A and Lacerda, AE and Barclay, J and Williamson, MP and Fox, M and Rees, M and Lee, JH},
      title = {Molecular characterization of a neuronal low-voltage-activated T-type calcium channel},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1998},
      volume = {391},
      number = {6670},
      pages = {896-900}
    }
    
    Pessoa, L., McKenna, M., Gutierrez, E. & Ungerleider, L. Neural processing of emotional faces requires attention {2002} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {99}({17}), pp. {11458-11463} 
    article DOI  
    Abstract: Attention gates the processing of stimuli relatively early in visual cortex. Yet, existing data suggest that emotional stimuli activate brain regions automatically, largely immune from attentional control. To resolve this puzzle, we used functional magnetic resonance imaging to first measure activation in regions that responded differentially to faces with emotional expressions (fearful and happy) compared with neutral faces. We then measured the modulation of these responses by attention, using a competing task with a high attentional load. Contrary to the prevailing view, all brain regions responding differentially to emotional faces, including the amygdala, did so only when sufficient attentional resources were available to process the faces. Thus, the processing of facial expression appears to be under top-down control.
    BibTeX:
    @article{Pessoa2002,
      author = {Pessoa, L and McKenna, M and Gutierrez, E and Ungerleider, LG},
      title = {Neural processing of emotional faces requires attention},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {2002},
      volume = {99},
      number = {17},
      pages = {11458-11463},
      doi = {{10.1073/pnas.172403899}}
    }
    
    Peterson, B., Vohr, B., Staib, L., Cannistraci, C., Dolberg, A., Schneider, K., Katz, K., Westerveld, M., Sparrow, S., Anderson, A., Duncan, C., Makuch, R., Gore, J. & Ment, L. Regional brain volume abnormalities and long-term cognitive outcome in preterm infants {2000} JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
    Vol. {284}({15}), pp. {1939-1947} 
    article  
    Abstract: Context Preterm infants have a high prevalence of long-term cognitive and behavioral disturbances. However, it is not known whether the stresses associated with premature birth disrupt regionally specific brain maturation or whether abnormalities in brain structure contribute to cognitive deficits. Objective To determine whether regional brain volumes differ between term and preterm children and to examine the association of regional brain volumes in prematurely born children with long-term cognitive outcomes. Design and Setting Case-control study conducted in 1998 and 1999 at 2 US university medical schools. Participants A consecutive sample of 25 eight-year-old preterm children recruited from a longitudinal follow-up study of preterm infants and 39 term control children who were recruited from the community and who were comparable with the preterm children in age, sex, maternal education, and minority status. Main Outcome Measures Volumes of cortical subdivisions, Ventricular system, cerebellum, basal ganglia, corpus callosum, amygdala, and hippocampus, derived from structural magnetic resonance imaging scans and compared between preterm and term children; correlations of regional brain volumes with cognitive measures (at age 8 years) and perinatal variables among preterm children. Results Regional cortical volumes were significantly smaller in the preterm children, most prominently in sensorimotor regions (difference: left, 14.6 right, 14.3% [P<.001 for both]) but also in premotor (left, 11.2 right, 12.6% [P<.001 for both]), midtemporal (left, 7.4% [P=.01]; right, 10.2% [P<.001]), parieto-occipital (left, 7.9% [P=.01]; right, 7.4% [P=.005]), and subgenual (left, 8.9% [P=.03]; right, 11.7% [P=.01])cortices. Preterm children's brain volumes were significantly larger (by 105.7271.6 in the occipital and temporal horns of the ventricles (P<.001 for all) and smaller in the cerebellum (6.7 P=.02), basal ganglia (11.413.8 P less than or equal to.005), amygdala (left, 20.2% [P=.001]; right, 30.0% [P<.001]), hippocampus (left, 16.0% [P=.001]; right, 12.0% [P=.007]), and corpus callosum (13.135.2 P less than or equal to.01 for all). Volumes of sensorimotor and midtemporal cortices were associated positively with full-scale, verbal, and performance IQ scores (P<.01 for all). Conclusions Our data indicate that preterm birth is associated with regionally specific, long-term reductions in brain volume and that morphological abnormalities are, in turn, associated with poorer cognitive outcome.
    BibTeX:
    @article{Peterson2000,
      author = {Peterson, BS and Vohr, B and Staib, LH and Cannistraci, CJ and Dolberg, A and Schneider, KC and Katz, KH and Westerveld, M and Sparrow, S and Anderson, AW and Duncan, CC and Makuch, RW and Gore, JC and Ment, LR},
      title = {Regional brain volume abnormalities and long-term cognitive outcome in preterm infants},
      journal = {JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION},
      publisher = {AMER MEDICAL ASSOC},
      year = {2000},
      volume = {284},
      number = {15},
      pages = {1939-1947}
    }
    
    Pezawas, L., Meyer-Lindenberg, A., Drabant, E., Verchinski, B., Munoz, K., Kolachana, B., Egan, M., Mattay, V., Hariri, A. & Weinberger, D. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression {2005} NATURE NEUROSCIENCE
    Vol. {8}({6}), pp. {828-834} 
    article DOI  
    Abstract: Carriers of the short allele of a functional 5' promoter polymorphism of the serotonin transporter gene have increased anxiety-related temperamental traits, increased amygdala reactivity and elevated risk of depression. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to elucidate neural mechanisms underlying this complex genetic association. Morphometrical analyses showed reduced gray matter volume in short-allele carriers in limbic regions critical for processing of negative emotion, particularly perigenual cingulate and amygdala. Functional analysis of those regions during perceptual processing of fearful stimuli demonstrated tight coupling as a feedback circuit implicated in the extinction of negative affect. Short-allele carriers showed relative uncoupling of this circuit. Furthermore, the magnitude of coupling inversely predicted almost 30% of variation in temperamental anxiety. These genotype-related alterations in anatomy and function of an amygdala-cingulate feedback circuit critical for emotion regulation implicate a developmental, systems- level mechanism underlying normal emotional reactivity and genetic susceptibility for depression.
    BibTeX:
    @article{Pezawas2005,
      author = {Pezawas, L and Meyer-Lindenberg, A and Drabant, EM and Verchinski, BA and Munoz, KE and Kolachana, BS and Egan, MF and Mattay, VS and Hariri, AR and Weinberger, DR},
      title = {5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2005},
      volume = {8},
      number = {6},
      pages = {828-834},
      doi = {{10.1038/nn1463}}
    }
    
    Phan, K., Wager, T., Taylor, S. & Liberzon, I. Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI {2002} NEUROIMAGE
    Vol. {16}({2}), pp. {331-348} 
    article DOI  
    Abstract: Neuroimaging studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have begun to describe the functional neuroanatomy of emotion. Taken separately, specific studies vary in task dimensions and in type(s) of emotion studied and are limited by statistical power and sensitivity. By examining findings across studies, we sought to determine if common or segregated patterns of activations exist across various emotional tasks. We reviewed 55 PET and fMRI activation studies (yielding 761 individual peaks) which investigated emotion in healthy subjects. Peak activation coordinates were transformed into a standard space and plotted onto canonical 3-D brain renderings. We divided the brain into 20 non-overlapping regions, and characterized each region by its responsiveness across individual emotions (positive, negative, happiness, fear, anger, sadness, disgust), to different induction methods (visual, auditory, recall/imagery), and in emotional tasks with and without cognitive demand. Our review yielded the following summary observations: (1) The medial prefrontal cortex had a general role in emotional processing; (2) fear specifically engaged the amygdala; (3) sadness was associated with activity in the subcallosal cingulate; (4) emotional induction by visual stimuli activated the occipital cortex and the amygdala; (5) induction by emotional recall/imagery recruited the anterior cingulate and insula; (6) emotional tasks with cognitive demand also involved the anterior cingulate and insula. This review provides a critical comparison of findings across individual studies and suggests that separate brain regions are involved in different aspects of emotion. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Phan2002,
      author = {Phan, KL and Wager, T and Taylor, SF and Liberzon, I},
      title = {Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI},
      journal = {NEUROIMAGE},
      publisher = {ACADEMIC PRESS INC ELSEVIER SCIENCE},
      year = {2002},
      volume = {16},
      number = {2},
      pages = {331-348},
      doi = {{10.1006/nimg.2002.1087}}
    }
    
    Phelps, E. Emotion and cognition: Insights from studies of the human amygdala {2006} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {57}, pp. {27-53} 
    article DOI  
    Abstract: Traditional approaches to the study of cognition emphasize an information-processing view that has generally excluded emotion. In contrast, the recent emergence of cognitive neuroscience as an inspiration for understanding human cognition has highlighted its interaction with emotion. This review explores insights into the relations between emotion and cognition that have resulted from studies of the human amygdala. Five topics are explored: emotional learning, emotion and memory, emotion's influence on attention and perception, processing emotion in social stimuli, and changing emotional responses. Investigations into the neural systems underlying human behavior demonstrate that the mechanisms of emotion and cognition are intertwined from early perception to reasoning. These findings suggest that the classic division between the study of emotion and cognition may be unrealistic and that an understanding of human cognition requires the consideration of emotion.
    BibTeX:
    @article{Phelps2006,
      author = {Phelps, EA},
      title = {Emotion and cognition: Insights from studies of the human amygdala},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      publisher = {ANNUAL REVIEWS},
      year = {2006},
      volume = {57},
      pages = {27-53},
      doi = {{10.1146/annurev.psych.56.091103.070234}}
    }
    
    Phelps, E., Delgado, M., Nearing, K. & LeDoux, J. Extinction learning in humans: Role of the amygdala and vmPFC {2004} NEURON
    Vol. {43}({6}), pp. {897-905} 
    article  
    Abstract: Understanding how fears are acquired is an important step in translating basic research to the treatment of fear-related disorders. However, understanding how learned fears are diminished may be even more valuable. We explored the neural mechanisms of fear extinction in humans. Studies of extinction in nonhuman animals have focused on two interconnected brain regions: the amygdala and the ventral medial prefrontal cortex (vmPFC). Consistent with animal models suggesting that the amygdala is important for both the acquisition and extinction of conditioned fear, amygdala activation was correlated across subjects with the conditioned response in both acquisition and early extinction. Activation in the vmPFC (subgenual anterior cingulate) was primarily linked to the expression of fear learning during a delayed test of extinction, as might have been expected from studies demonstrating this region is critical for the retention of extinction. These results provide evidence that the mechanisms of extinction learning may be preserved across species.
    BibTeX:
    @article{Phelps2004,
      author = {Phelps, EA and Delgado, MR and Nearing, KI and LeDoux, JE},
      title = {Extinction learning in humans: Role of the amygdala and vmPFC},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2004},
      volume = {43},
      number = {6},
      pages = {897-905}
    }
    
    Phelps, E. & LeDoux, J. Contributions of the amygdala to emotion processing: From animal models to human behavior {2005} NEURON
    Vol. {48}({2}), pp. {175-187} 
    article DOI  
    Abstract: Research on the neural systems underlying emotion in animal models over the past two decades has implicated the amygdala in fear and other emotional processes. This work stimulated interest in pursuing the brain mechanisms of emotion in humans. Here, we review research on the role of the amygdala in emotional processes in both animal models and humans. The review is not exhaustive, but it highlights five major research topics that illustrate parallel roles for the amygdala in humans and other animals, including implicit emotional learning and memory, emotional modulation of memory, emotional influences on attention and perception, emotion and social behavior, and emotion inhibition and regulation.
    BibTeX:
    @article{Phelps2005,
      author = {Phelps, EA and LeDoux, JE},
      title = {Contributions of the amygdala to emotion processing: From animal models to human behavior},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2005},
      volume = {48},
      number = {2},
      pages = {175-187},
      doi = {{10.1016/j.neuron.2005.09.025}}
    }
    
    Phelps, E., O'Connor, K., Cunningham, W., Funayama, E., Gatenby, J., Gore, J. & Banaji, M. Performance on indirect measures of race evaluation predicts amygdala activation {2000} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {12}({5}), pp. {729-738} 
    article  
    Abstract: We used fMRI to explore the neural substrates involved in the unconscious evaluation of Black and White social groups. Specifically, we focused on the amygdala, a subcortical structure known to play a role in emotional learning and evaluation. In Experiment 1, White American subjects observed faces of unfamiliar Black and White males. The strength of amygdala activation to Black-versus-White faces was correlated with two indirect (unconscious) measures of race evaluation (Implicit Association Test [IAT] and potentiated startle), but not with the direct (conscious) expression of race attitudes. In Experiment 2, these patterns were not obtained when the stimulus faces belonged to familiar and positively regarded Black and White individuals. Together, these results suggest that amygdala and behavioral responses to Black-versus-White faces in White subjects reflect cultural evaluations of social groups modified by individual experience.
    BibTeX:
    @article{Phelps2000,
      author = {Phelps, EA and O'Connor, KJ and Cunningham, WA and Funayama, ES and Gatenby, JC and Gore, JC and Banaji, MR},
      title = {Performance on indirect measures of race evaluation predicts amygdala activation},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      publisher = {M I T PRESS},
      year = {2000},
      volume = {12},
      number = {5},
      pages = {729-738}
    }
    
    Phelps, E., O'Connor, K., Gatenby, J., Gore, J., Grillon, C. & Davis, M. Activation of the left amygdala to a cognitive representation of fear {2001} NATURE NEUROSCIENCE
    Vol. {4}({4}), pp. {437-441} 
    article  
    Abstract: We examined the neural substrates involved when subjects encountered an event linked verbally, but not experientially, to an aversive outcome. This instructed fear task models a primary way humans learn about the emotional nature of events. Subjects were told that one stimulus (threat) represents an aversive event (a shock may be given), whereas another (safe) represents safety (no shock will be given). Using functional magnetic resonance imaging (fMRI), activation of the left amygdala was observed in response to threat versus safe conditions, which correlated with the expression of the fear response as measured by skin conductance. Additional activation observed in the insular cortex is proposed to be involved in conveying a cortical representation of fear to the amygdala. These results suggest that the neural substrates that support conditioned fear across species have a similar but somewhat different role in more abstract representations of fear in humans.
    BibTeX:
    @article{Phelps2001,
      author = {Phelps, EA and O'Connor, KJ and Gatenby, JC and Gore, JC and Grillon, C and Davis, M},
      title = {Activation of the left amygdala to a cognitive representation of fear},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {2001},
      volume = {4},
      number = {4},
      pages = {437-441}
    }
    
    Phillips, M., Drevets, W., Rauch, S. & Lane, R. Neurobiology of emotion perception I: The neural basis of normal emotion perception {2003} BIOLOGICAL PSYCHIATRY
    Vol. {54}({5}), pp. {504-514} 
    article DOI  
    Abstract: There is at present limited understanding of the neurobiological basis of the different processes underlying emotion perception. We have aimed to identify potential neural correlates of three processes suggested by appraisalist theories as important for emotion perception: 1) the identification of the emotional significance of a stimulus; 2) the production of an affective state in response to 1; and 3) the regulation of the affective state. In a critical review, we have examined findings from recent animal, human lesion, and functional neuroimaging studies. Findings from these studies indicate that these processes may be dependent upon the functioning of two neural systems: a ventral system, including the amygdala, insula, ventral striatum, and ventral regions of the anterior cingulate gyrus and prefrontal cortex, predominantly important for processes 1 and 2 and automatic regulation of emotional responses; and a dorsal system, including the hippocampus and dorsal regions of anterior cingulate gyrus and prefrontal cortex, predominantly important for process 3. We suggest that the extent to which a stimulus is identified as emotive and is associated with the production of an affective state may be dependent upon levels of activity within these two neural systems.
    BibTeX:
    @article{Phillips2003,
      author = {Phillips, ML and Drevets, WC and Rauch, SL and Lane, R},
      title = {Neurobiology of emotion perception I: The neural basis of normal emotion perception},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2003},
      volume = {54},
      number = {5},
      pages = {504-514},
      doi = {{10.1016/S0006-3223(03)00168-9}}
    }
    
    Phillips, M., Drevets, W., Rauch, S. & Lane, R. Neurobiology of emotion perception II: Implications for major psychiatric disorders {2003} BIOLOGICAL PSYCHIATRY
    Vol. {54}({5}), pp. {515-528} 
    article DOI  
    Abstract: To date, there has been little investigation of the neurobiological basis of emotion processing abnormalities in psychiatric populations. We have previously discussed two neural systems: 1) a ventral system, including the amygdala, insula, ventral striatum, ventral anterior cingulate gyrus, and prefrontal cortex, for identification of the emotional significance of a stimulus, production of affective states, and automatic regulation of emotional responses; and 2) a dorsal system, including the hippocampus, dorsal anterior cingulate gyrus, and prefrontal cortex, for the effortful regulation of affective states and subsequent behavior. In this critical review, we have examined evidence from studies employing a variety of techniques for distinct patterns of structural and Junctional abnormalities in these neural systems in schizophrenia, bipolar disorder, and major depressive disorder. In each psychiatric disorder, the pattern of abnormalities may be associated with specific symptoms, including emotional flattening, anhedonia, and persecutory delusions in schizophrenia, prominent mood swings, emotional lability and distractibility in bipolar disorder during depression and mania, and with depressed mood and anhedonia in major depressive disorder. We suggest that distinct patterns of structural and functional abnormalities in neural systems important for emotion processing are associated with specific symptoms of schizophrenia and bipolar and major depressive disorder.
    BibTeX:
    @article{Phillips2003a,
      author = {Phillips, ML and Drevets, WC and Rauch, SL and Lane, R},
      title = {Neurobiology of emotion perception II: Implications for major psychiatric disorders},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2003},
      volume = {54},
      number = {5},
      pages = {515-528},
      doi = {{10.1016/S0006-3223(03)00171-9}}
    }
    
    Phillips, M., Young, A., Scott, S., Calder, A., Andrew, C., Giampietro, V., Williams, S., Bullmore, E., Brammer, M. & Gray, J. Neural responses to facial and vocal expressions of fear and disgust {1998} PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {265}({1408}), pp. {1809-1817} 
    article  
    Abstract: Neuropsychological studies report more impaired responses to facial expressions of fear than disgust in people with amygdala lesions, and vice versa in people with Huntington's disease. Experiments using functional magnetic resonance imaging (fMRI) have confirmed the role of the amygdala in the response to fearful faces and have implicated the anterior insula in the response to facial expressions of disgust. We used fMRI to extend these studies to the perception of fear and disgust from both facial and vocal expressions. Consistent with neuropsychological findings, both types of fearful stimuli activated the amygdala. Facial expressions of disgust activated the anterior insula and the caudate-putamen; vocal expressions of disgust did not significantly activate either of these regions. All four types of stimuli activated the superior temporal gyrus. Our findings therefore (i) support the differential localization of the neural substrates of fear and disgust; (ii) confirm the involvement of the amygdala in the emotion of fear, whether evoked by facial or vocal expressions; (iii) confirm the involvement of the anterior insula and the striatum in reactions to facial expressions of disgust; and (iv) suggest a possible general role for the perception of emotional expressions for the superior temporal gyrus.
    BibTeX:
    @article{Phillips1998,
      author = {Phillips, ML and Young, AW and Scott, SK and Calder, AJ and Andrew, C and Giampietro, V and Williams, SCR and Bullmore, ET and Brammer, M and Gray, JA},
      title = {Neural responses to facial and vocal expressions of fear and disgust},
      journal = {PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      publisher = {ROYAL SOC LONDON},
      year = {1998},
      volume = {265},
      number = {1408},
      pages = {1809-1817}
    }
    
    Phillips, M., Young, A., Senior, C., Brammer, M., Andrew, C., Calder, A., Bullmore, E., Perrett, D., Rowland, D., Williams, S., Gray, J. & David, A. A specific neural substrate for perceiving facial expressions of disgust {1997} NATURE
    Vol. {389}({6650}), pp. {495-498} 
    article  
    Abstract: Recognition of facial expressions is critical to our appreciation of the social and physical environment, with separate emotions having distinct facial expressions(1). Perception of fearful facial expressions has been extensively studied, appearing to depend upon the amygdala(2-6). Disgust-literally `bad taste'-is another important emotion, with a distinct evolutionary history(7), and is conveyed by a characteristic facial expression(8-10). We have used functional magnetic resonance imaging (MRI) to examine the neural substrate for perceiving disgust expressions. Normal volunteers were presented with faces showing mild or strong disgust or fear. Cerebral activation in response to these stimuli was contrasted with that for neutral faces. Results for fear generally confirmed previous positron emission tomography findings of amygdala involvement. Both strong and mild expressions of disgust activated anterior insular cortex but not the amygdala; strong disgust also activated structures linked to a limbic cortico-striatal-thalamic circuit. The anterior insula is known to be involved in responses to offensive tastes. The neural response to facial expressions of disgust in others is thus closely related to appraisal of distasteful stimuli.
    BibTeX:
    @article{Phillips1997,
      author = {Phillips, ML and Young, AW and Senior, C and Brammer, M and Andrew, C and Calder, AJ and Bullmore, ET and Perrett, DI and Rowland, D and Williams, SCR and Gray, JA and David, AS},
      title = {A specific neural substrate for perceiving facial expressions of disgust},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1997},
      volume = {389},
      number = {6650},
      pages = {495-498}
    }
    
    PHILLIPS, R. & LEDOUX, J. DIFFERENTIAL CONTRIBUTION OF AMYGDALA AND HIPPOCAMPUS TO CUED AND CONTEXTUAL FEAR CONDITIONING {1992} BEHAVIORAL NEUROSCIENCE
    Vol. {106}({2}), pp. {274-285} 
    article  
    Abstract: The contribution of the amygdala and hippocampus to the acquisition of conditioned fear responses to a cue (a tone paired with footshock) and to context (background stimuli continuously present in the apparatus in which tone-shock pairings occurred) was examined in rats. In unoperated controls, responses to the cue conditioned faster and were more resistant to extinction than were responses to contextual stimuli. Lesions of the amygdala interfered with the conditioning of fear responses to both the cue and the context, whereas lesions of the hippocampus interfered with conditioning to the context but not to the cue. The amygdala is thus involved in the conditioning of fear responses to simple, modality-specific conditioned stimuli as well as to complex, polymodal stimuli, whereas the hippocampus is only involved in fear conditioning situations involving complex, polymodal events. These findings suggest an associative role for the amygdala and a sensory relay role for the hippocampus in fear conditioning.
    BibTeX:
    @article{PHILLIPS1992,
      author = {PHILLIPS, RG and LEDOUX, JE},
      title = {DIFFERENTIAL CONTRIBUTION OF AMYGDALA AND HIPPOCAMPUS TO CUED AND CONTEXTUAL FEAR CONDITIONING},
      journal = {BEHAVIORAL NEUROSCIENCE},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1992},
      volume = {106},
      number = {2},
      pages = {274-285}
    }
    
    Pich, E., Pagliusi, S., Tessari, M., TalabotAyer, D., vanHuijsduijnen, R. & Chiamulera, C. Common neural substrates for the addictive properties of nicotine and cocaine {1997} SCIENCE
    Vol. {275}({5296}), pp. {83-86} 
    article  
    Abstract: Regional brain activation was assessed by mapping of Fos-related protein expression in rats trained to self-administration of intravenous nicotine and cocaine. Both drugs produced specific overlapping patterns of activation in the shell and the core of the nucleus accumbens, medial prefrontal cortex, and medial caudate areas, but not in the amygdala. Thus, the reinforcing properties of cocaine and nicotine map on selected structures of the terminal fields of the mesocorticolimbic dopamine system, supporting the idea that common substrates for these addictive drugs exist.
    BibTeX:
    @article{Pich1997,
      author = {Pich, EM and Pagliusi, SR and Tessari, M and TalabotAyer, D and vanHuijsduijnen, RH and Chiamulera, C},
      title = {Common neural substrates for the addictive properties of nicotine and cocaine},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {1997},
      volume = {275},
      number = {5296},
      pages = {83-86}
    }
    
    Pierce, K., Muller, R., Ambrose, J., Allen, G. & Courchesne, E. Face processing occurs outside the fusiform `face area' in autism: evidence from functional MRI {2001} BRAIN
    Vol. {124}({Part 10}), pp. {2059-2073} 
    article  
    Abstract: Processing the human face is at the focal point of most social interactions, yet this simple perceptual task is difficult for individuals with autism, a population that spends limited amounts of time engaged in face-to-face eye contact or social interactions in general. Thus, the study of face processing in autism is not only important because it may be integral to understanding the social deficits of this disorder, but also, because it provides a unique opportunity to study experiential factors related to the functional specialization of normal face processing. In short, autism may be one of the only disorders where affected individuals spend reduced amounts of time engaged in face processing from birth. Using functional MRI, haemodynamic responses during a face perception task were compared between adults with autism and normal control subjects. Four regions of interest (ROIs), the fusiform gyrus (FG), inferior temporal gyrus, middle temporal gyrus and amygdala were manually traced on non-spatially normalized images and the percentage ROI active was calculated for each subject. Analyses in Talairach space were also performed. Overall results revealed either abnormally weak or no activation in FG in autistic patients, as well as significantly reduced activation in the inferior occipital gyrus, superior temporal sulcus and amygdala. Anatomical abnormalities, in contrast, were present only in the amygdala in autistic patients, whose mean volume was significantly reduced as compared with normals. Reaction time and accuracy measures were not different between groups. Thus, while autistic subjects could perform the face perception task, none of the regions supporting face processing in normals were found to be significantly active in the autistic subjects. Instead, in every autistic patient, faces maximally activated aberrant and individual-specific neural sites (e.g. frontal cortex, primary visual cortex, etc.), which was in contrast to the 100% consistency of maximal activation within the traditional fusiform face area (FFA) for every normal subject. It appears that, as compared with normal individuals, autistic individuals `see' faces utilizing different neural systems, with each patient doing so via a unique neural circuitry. Such a pattern of individual-specific, scattered activation seen in autistic patients in contrast to the highly consistent FG activation seen in normals, suggests that experiential factors do indeed play a role in the normal development of the FFA.
    BibTeX:
    @article{Pierce2001,
      author = {Pierce, K and Muller, RA and Ambrose, J and Allen, G and Courchesne, E},
      title = {Face processing occurs outside the fusiform `face area' in autism: evidence from functional MRI},
      journal = {BRAIN},
      publisher = {OXFORD UNIV PRESS},
      year = {2001},
      volume = {124},
      number = {Part 10},
      pages = {2059-2073}
    }
    
    Pirker, S., Schwarzer, C., Wieselthaler, A., Sieghart, W. & Sperk, G. GABA(A) receptors: Immunocytochemical distribution of 13 subunits in the adult rat brain {2000} NEUROSCIENCE
    Vol. {101}({4}), pp. {815-850} 
    article  
    Abstract: GABA(A) receptors are ligand-operated chloride channels assembled from five subunits in a heteropentameric manner. Using immunocytochemistry, we investigated the distribution of GABA(A) receptor subunits deriving from 13 different genes (alpha1-alpha6, beta1-beta3, gamma1-gamma3 and delta) in the adult rat brain. Subunit alpha1-, beta1-, beta2-, beta3- and gamma2-immunoreactivities were found throughout the brain, although differences in their distribution were observed. Subunit alpha2-, alpha3-, alpha4-, alpha5-, alpha6-, gamma1- and delta -immunoreactivities were more confined to certain brain areas. Thus, alpha2-subunit-immunoreactivity was preferentially located in forebrain areas and the cerebellum. Subunit alpha6-immunoreactivity was only present in granule cells of the cerebellum and the cochlear nucleus, and subunit gamma1-immunoreactivity was preferentially located in the central and medial amygdaloid nuclei, in pallidal areas, the substantia nigra pars reticulata and the inferior olive. The alpha5-subunit-immunoreactivity was strongest in Ammon's horn, the olfactory bulb and hypothalamus. In contrast, alpha4-subunit-immunoreactivity was detected in the thalamus, dentate gyrus, olfactory tubercle and basal ganglia. Subunit alpha3-immunoreactivity was observed in the glomerular and external plexiform layers of the olfactory bulb, in the inner layers of the cerebral cortex, the reticular thalamic nucleus, the zonal and superficial layers of the superior colliculus, the amygdala and cranial nerve nuclei. Only faint subunit gamma3-immunoreactivity was detected in most areas; it was darkest in midbrain and pontine nuclei. Subunit delta -immunoreactivity was frequently co-distributed with alpha4 subunit-immunoreactivity, e.g. in the thalamus, striatum, outer layers of the cortex and dentate molecular layer. Striking examples of complementary distribution of certain subunit-immunoreactivities were observed. Thus, subunit alpha2-, alpha4-, beta1-, beta3- and delta -immunoreactivities were considerably more concentrated in the neostriatum than in the pallidum and entopeduncular nucleus. In contrast, labeling for the alpha1-, beta2-, gamma1- and gamma2-subunits prevailed in the pallidum compared to the striatum. With the exception of the reticular thalamic nucleus, which was prominently stained for subunits alpha3, beta1, beta3 and gamma2, most thalamic nuclei were rich in alpha1-, alpha4-, beta2- and delta -immunoreactivities. Whereas the dorsal lateral geniculate nucleus was strongly immunoreactive for subunits alpha4, beta2 and delta, the ventral lateral geniculate nucleus was predominantly labeled for subunits alpha2, alpha3, beta1, beta3 and gamma2; subunit alpha1- and alpha5-immunoreactivities were about equally distributed in both areas. In most hypothalamic areas, immunoreactivities for subunits alpha1, alpha2, beta1, beta2 and beta3 were observed. In the supraoptic nucleus, staining of conspicuous dendritic networks with subunit alpha1, alpha2, beta2, and gamma2 antibodies was contrasted by perykarya labeled for alpha5-, beta1- and delta -immunoreactivities. Among all brain regions, the median emminence was most heavily labeled for subunit beta2-immunoreactivity. In most pontine and cranial nerve nuclei and in the medulla, only subunit alpha1-, beta2- and gamma2-immunoreactivities were strong, whereas the inferior olive was significantly labeled only for subunits beta1, gamma1 and gamma2. In this study, a highly heterogeneous distribution of 13 different GABA(A) receptor subunit-immunoreactivities was observed. This distribution and the apparently typical patterns of co-distribution of these GABA(A) receptor subunits support the assumption of multiple, differently assembled GABA(A) receptor subtypes and their heterogeneous distribution within the adult rat brain. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Pirker2000,
      author = {Pirker, S and Schwarzer, C and Wieselthaler, A and Sieghart, W and Sperk, G},
      title = {GABA(A) receptors: Immunocytochemical distribution of 13 subunits in the adult rat brain},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2000},
      volume = {101},
      number = {4},
      pages = {815-850}
    }
    
    Pitkanen, A., Pikkarainen, M., Nurminen, N. & Ylinen, A. Reciprocal connections between the amygdala and the hippocampal formation, perirhinal cortex, and postrhinal cortex in rat - A review {2000}
    Vol. {911}PARAHIPPOCAMPAL REGION - IMPLICATIONS FOR NEUROLOGICAL AND PSYCHIATRIC DISEASES , pp. {369-391} 
    inproceedings  
    Abstract: Recent anterograde and retrograde studies in the rat have provided detailed information on the origin and termination of the interconnections between the amygdaloid complex and the hippocampal formation and parahippocampal areas (including areas 35 and 36 of the perirhinal cortex and the postrhinal cortex), The most substantial inputs to the amygdala originate in the rostral half of the entorhinal cortex, the temporal end of the CA1 subfield and subiculum, and areas 35 and 36 of the perirhinal cortex, The amygdaloid nuclei receiving the heaviest inputs are the lateral, basal, accessory basal, and central nuclei as well as the amygdalohippocampal area, The heaviest projections from the amygdala to the hippocampal formation and the parahippocampal areas originate in the lateral, basal, accessory basal, and posterior cortical nuclei, These pathways terminate in the rostral half of the entorhinal cortex, the temporal end of the CA3 and CA1 subfields or the subiculum, the parasubiculum, areas 35 and 36 of the perirhinal cortex, and the postrhinal cortex, The connectional data are summarized and the underlying principles of organization of these projections are discussed.
    BibTeX:
    @inproceedings{Pitkanen2000,
      author = {Pitkanen, A and Pikkarainen, M and Nurminen, N and Ylinen, A},
      title = {Reciprocal connections between the amygdala and the hippocampal formation, perirhinal cortex, and postrhinal cortex in rat - A review},
      booktitle = {PARAHIPPOCAMPAL REGION - IMPLICATIONS FOR NEUROLOGICAL AND PSYCHIATRIC DISEASES },
      publisher = {NEW YORK ACAD SCIENCES},
      year = {2000},
      volume = {911},
      pages = {369-391},
      note = {Conference on Hippocampal Region - Basic Science and Clinical Implications, BALTIMORE, MARYLAND, SEP 23-26, 1999}
    }
    
    Pitkanen, A., Savander, V. & LeDoux, J. Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala {1997} TRENDS IN NEUROSCIENCES
    Vol. {20}({11}), pp. {517-523} 
    article  
    Abstract: The amygdala is located in the medial aspects of the temporal lobe. In spite of the fact that the amygdala has been implicated in a variety of functions, ranging from attention to memory to emotion, it has not attracted neuroscientists to the same extent as its laminated neighbours, in particular the hippocampus and surrounding cortex. However, recently, principles of information processing within the amygdala, particularly in the rat, have begun to emerge from anatomical, physiological and behavioral studies. These findings suggest that after the stimulus enters the amygdala, the highly organized intra-amygdaloid circuitries provide a pathway by which the representation of a stimulus becomes distributed in parallel to various amygdaloid nuclei. As a consequence,the stimulus representation may become modulated by different functional systems, such as those mediating memories from past experience or knowledge about ongoing homeostatic states. The amygdaloid output nuclei, especially the central nucleus, receive convergent information from several other amygdaloid regions and generate behavioral responses that presumably reflect the sum of neuronal activity produced by different amygdaloid nuclei.
    BibTeX:
    @article{Pitkanen1997,
      author = {Pitkanen, A and Savander, V and LeDoux, JE},
      title = {Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala},
      journal = {TRENDS IN NEUROSCIENCES},
      publisher = {ELSEVIER SCI LTD},
      year = {1997},
      volume = {20},
      number = {11},
      pages = {517-523}
    }
    
    POLLARD, H., CHARRIAUTMARLANGUE, C., CANTAGREL, S., REPRESA, A., ROBAIN, O., MOREAU, J. & BENARI, Y. KAINATE-INDUCED APOPTOTIC CELL-DEATH IN HIPPOCAMPAL-NEURONS {1994} NEUROSCIENCE
    Vol. {63}({1}), pp. {7-18} 
    article  
    Abstract: We have examined the role apoptosis plays in epileptic brain damage using intra-amygdaloid injection of kainate. With the silver staining technique of Gallyas, argyrophylic (dying) neurons were observed, a few hours after the injection, in the amygdala and in the vulnerable pyramidal neurons of the hippocampal CA3 region. In both areas, cell death has apoptotic features, including: (i) nuclear chromatin condensation and marginalization with light and electron microscopy; (ii) DNA fragmentation with a typical ladder pattern on agarose gel electrophoresis; (iii) positive nuclear labelling with a selective in situ DNA fragmentation staining method. Combined in situ DNA labelling and silver staining showed that the DNA fragmentation occurred in dying neurons. CA1 or granule cells which do not degenerate following intra-amygdaloid injection of kainate were not stained with the in situ DNA labelling or the argyrophylic technique. Administration of diazepam blocked the kainate-induced seizures and prevented DNA fragmentation in CA3 but not in the amygdala. Therefore, apoptosis contributes to the local and distant damage induced by kainate.
    BibTeX:
    @article{POLLARD1994,
      author = {POLLARD, H and CHARRIAUTMARLANGUE, C and CANTAGREL, S and REPRESA, A and ROBAIN, O and MOREAU, J and BENARI, Y},
      title = {KAINATE-INDUCED APOPTOTIC CELL-DEATH IN HIPPOCAMPAL-NEURONS},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1994},
      volume = {63},
      number = {1},
      pages = {7-18}
    }
    
    POMPEIANO, M., PALACIOS, J. & MENGOD, G. DISTRIBUTION OF THE SEROTONIN 5-HT2 RECEPTOR FAMILY MESSENGER-RNAS - COMPARISON BETWEEN 5-HT(2A) AND 5-HT(2C) RECEPTORS {1994} MOLECULAR BRAIN RESEARCH
    Vol. {23}({1-2}), pp. {163-178} 
    article  
    Abstract: Because of their similarities, serotonin 5-HT2, 5-HT1C, and the recently described 5-HT2F receptors have been classified as members of the 5-HT2 receptor family, and they have been renamed 5-HT2A, 5-HT2C and 5-HT2B, respectively. The regional distribution and cellular localization of mRNA coding for the members of 5-HT2 receptor family were investigated in consecutive tissue sections from the rat brain by in situ hybridization histochemistry. No evidence for the expression of 5-HT2B receptor was found. High levels of 5-HT2A (formerly 5-HT2) receptor mRNA were observed only in few areas, as the frontal cortex, piriform cortex, ventro-caudal part of CA3, medial mammilary nucleus, the pontine nuclei and the motor cranial nerve nuclei in the brainstem, and the ventral horn of the spinal Cord. The distribution of 5-HT2A receptor mRNA is generally in good agreement with that of the corresponding binding sites, although discrepancies were sometimes observed. 5-HT2C (formerly 5-HT1C) mRNA was present at very high levels in the choroid plexuses. However, very high levels were also seen in many other brain regions, as the retrosplenial, piriform and entorhinal cortex, anterior olfactory nucleus, lateral septal nucleus, subthalamic nucleus, amygdala, subiculum and ventral part of CA3, lateral habenula, substantia nigra pars compacta, several brainstem nuclei and the whole grey matter of the spinal cord. These results confirm and extend previous observations that 5-HT2C receptor mRNA is present in many brain areas in addition to those autoradiographically shown to have the corresponding binding sites and that 5-HT2C receptor subtype is a principal 5-HT receptor in the brain. From the comparison between their distributions, 5-HT2A and 5-HT2C receptor mRNAs appeared to be expressed in distinct but overlapping sets of brain regions. Both mRNAs coexisted at high levels in the anterior olfactory nucleus, piriform cortex, endopiriform nucleus, claustrum, pyramidal cell layer of the ventral part of CA3, taenia tecta, substantia nigra pars compacta, and several brainstem nuclei. In other regions both mRNAs were present but with different distributions, as the caudate-putamen. These results are also discussed in relation to the physiological meaning of the existence of two so similar receptor subtypes in the brain.
    BibTeX:
    @article{POMPEIANO1994,
      author = {POMPEIANO, M and PALACIOS, JM and MENGOD, G},
      title = {DISTRIBUTION OF THE SEROTONIN 5-HT2 RECEPTOR FAMILY MESSENGER-RNAS - COMPARISON BETWEEN 5-HT(2A) AND 5-HT(2C) RECEPTORS},
      journal = {MOLECULAR BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1994},
      volume = {23},
      number = {1-2},
      pages = {163-178}
    }
    
    Poorkaj, P., Bird, T., Wijsman, E., Nemens, E., Garruto, R., Anderson, L., Andreadis, A., Wiederholt, W., Raskind, M. & Schellenberg, G. Tau is a candidate gene for chromosome 17 frontotemporal dementia {1998} ANNALS OF NEUROLOGY
    Vol. {43}({6}), pp. {815-825} 
    article  
    Abstract: Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17), a recently defined disease entity, is clinically characterized by personality changes sometimes associated with psychosis, hyperorality, and diminished speech output, disturbed executive function and nonfluent aphasia, bradykinesia, and rigidity. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, and amygdala. Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance is autosomal dominant and the gene has been regionally localized to 17q21-22 in a 2- to 4-centimorgan (cM) region flanked by markers D17S800 and D17S791. The gene for tau, the primary component of NFTs, is located in the same region of chromosome 17. Tau was evaluated as a candidate gene. Physical mapping studies place tau within 2 megabases or less of D17S791, but it is probably outside the D17S800-D17S791 FTDP-17 interval. DNA sequence analysis of tau coding regions in affected subjects from two FTDP-17 families revealed nine DNA sequence variants, eight of which were also identified in controls and are thus polymorphisms. A ninth variant ((Val)279(Met)) was found in one FTDP-17 family but not in the second FTDP-17 family. Three lines of evidence indicate that the (Val)279(Met) change is an FTDP-17 causative mutation. First, the mutation site is highly conserved, and a normal valine is found at this position in all three tau interrepeat sequences and in other microtubule associated protein tau homologues. Second, the mutation co-segregates with the disease in family A. Third, the mutation is not found in normal controls.
    BibTeX:
    @article{Poorkaj1998,
      author = {Poorkaj, P and Bird, TD and Wijsman, E and Nemens, E and Garruto, RM and Anderson, L and Andreadis, A and Wiederholt, WC and Raskind, M and Schellenberg, GD},
      title = {Tau is a candidate gene for chromosome 17 frontotemporal dementia},
      journal = {ANNALS OF NEUROLOGY},
      publisher = {LIPPINCOTT WILLIAMS & WILKINS},
      year = {1998},
      volume = {43},
      number = {6},
      pages = {815-825}
    }
    
    PORRINO, L., CRANE, A. & GOLDMANRAKIC, P. DIRECT AND INDIRECT PATHWAYS FROM THE AMYGDALA TO THE FRONTAL-LOBE IN RHESUS-MONKEYS {1981} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {198}({1}), pp. {121-136} 
    article  
    BibTeX:
    @article{PORRINO1981,
      author = {PORRINO, LJ and CRANE, AM and GOLDMANRAKIC, PS},
      title = {DIRECT AND INDIRECT PATHWAYS FROM THE AMYGDALA TO THE FRONTAL-LOBE IN RHESUS-MONKEYS},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1981},
      volume = {198},
      number = {1},
      pages = {121-136}
    }
    
    POTTER, E., SUTTON, S., DONALDSON, C., CHEN, R., PERRIN, M., LEWIS, K., SAWCHENKO, P. & VALE, W. DISTRIBUTION OF CORTICOTROPIN-RELEASING FACTOR-RECEPTOR MESSENGER-RNA EXPRESSION IN THE RAT-BRAIN AND PITUITARY {1994} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {91}({19}), pp. {8777-8781} 
    article  
    Abstract: Corticotropin-releasing factor (CRF) is a major hypophysiotropic peptide regulating pituitary-adrenal response to stress, and it is also widely expressed in the central nervous system. The recent cloning of cDNAs encoding the human ind rat CRF receptors has enabled us to map the distribution of cells expressing CRF receptor mRNA in rat brain and pituitary by in situ hybridization. Receptor expression in the forebrain is dominated by widespread signal throughout all areas of the neo-, olfactory, and hippocampal cortices. Other prominent sites of CRF receptor mRNA expression include subcortical limbic structures in the septal region and amygdala. In the diencephalon, low levels of expression are seen in a few discrete ventral thalamic and medial hypothalamic nuclei. CRF receptor expression in hypothalamic neurosecretory structures, including the paraventricular nucleus and median eminence, is generally low. In the brainstem, certain relay nuclei associated with the somatic (including trigeminal), auditory, vestibular, and visceral sensory systems, constituted prominent sites of CRF receptor mRNA expression. In addition, high levels of this transcript are present in the cerebellar cortex and deep nuclei, along with many precerebellar nuclei. In the pituitary, moderate levels of CRF receptor mRNA expression were detected throughout the intermediate lobe and in a subset of cells in the anterior lobe identified as corticotropes by concurrent immunolabeling. Overall, the central distribution of CRF receptor mRNA expression is similar to, though more expansive than, that of regions reported to bind CRF, and it shows limited overlap with loci expressing CRF-binding protein. Interestingly, CRF receptor mRNA is low or undetectable in several cell groups implicated as central sites of CRF action.
    BibTeX:
    @article{POTTER1994,
      author = {POTTER, E and SUTTON, S and DONALDSON, C and CHEN, R and PERRIN, M and LEWIS, K and SAWCHENKO, PE and VALE, W},
      title = {DISTRIBUTION OF CORTICOTROPIN-RELEASING FACTOR-RECEPTOR MESSENGER-RNA EXPRESSION IN THE RAT-BRAIN AND PITUITARY},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1994},
      volume = {91},
      number = {19},
      pages = {8777-8781}
    }
    
    PRICE, J. & AMARAL, D. AN AUTORADIOGRAPHIC STUDY OF THE PROJECTIONS OF THE CENTRAL NUCLEUS OF THE MONKEY AMYGDALA {1981} JOURNAL OF NEUROSCIENCE
    Vol. {1}({11}), pp. {1242-1259} 
    article  
    BibTeX:
    @article{PRICE1981,
      author = {PRICE, JL and AMARAL, DG},
      title = {AN AUTORADIOGRAPHIC STUDY OF THE PROJECTIONS OF THE CENTRAL NUCLEUS OF THE MONKEY AMYGDALA},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1981},
      volume = {1},
      number = {11},
      pages = {1242-1259}
    }
    
    Pruessner, J., Li, L., Serles, W., Pruessner, M., Collins, D., Kabani, N., Lupien, S. & Evans, A. Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: Minimizing the discrepancies between laboratories {2000} CEREBRAL CORTEX
    Vol. {10}({4}), pp. {433-442} 
    article  
    Abstract: Within the medial temporal lobe, both the hippocampus and amygdala are frequently targeted by researchers and clinicians for volumetric analysis based on magnetic resonance imaging (MRI), However, different data acquisition techniques, analysis software and anatomical boundaries have in the past made it difficult to compare results of MRI studies from different laboratories. In order to reduce these differences, a segmentation protocol was established with 40 healthy normal control subjects recently scanned in our laboratory, Data acquisition was performed with a three-dimensional gradient echo technique, and scans were corrected for non-uniformity and registered into standard stereotaxic space prior to segmentation. Volumetric analysis was performed manually using three-dimensional software that allows simultaneous analysis of sagittal, coronal and horizontal images. Intra- and inter-rater coefficients yielded correlation coefficients comparable with other protocols. The hippocampal volume was larger in the right hemisphere (3324 versus 3208 mm(3)), while no interhemispheric differences for the amygdala (1154 versus 1160 mm(3)) could be observed. Most importantly, results from recent segmentation protocols for hippocampus and amygdala seem to approach each other with regard to mean volumes and interhemispheric differences. This indicates that the advances in scanning technique, volume preparation and segmentation protocols allow a more precise definition of medial temporal lobe structures with MRI, and that results for mean volumes for hippocampus and amygdala from different laboratories will eventually become comparable.
    BibTeX:
    @article{Pruessner2000,
      author = {Pruessner, JC and Li, LM and Serles, W and Pruessner, M and Collins, DL and Kabani, N and Lupien, S and Evans, AC},
      title = {Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: Minimizing the discrepancies between laboratories},
      journal = {CEREBRAL CORTEX},
      publisher = {OXFORD UNIV PRESS INC},
      year = {2000},
      volume = {10},
      number = {4},
      pages = {433-442}
    }
    
    Puelles, L., Kuwana, E., Puelles, E., Bulfone, A., Shimamura, K., Keleher, J., Smiga, S. & Rubenstein, J. Pallial and subpallial derivatives in the embryonic chick and mouse telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6, and Tbr-1 {2000} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {424}({3}), pp. {409-438} 
    article  
    Abstract: Pallial and subpallial morphological subdivisions of the developing chicken telencephalon were examined by means of gene markers, compared with their expression pattern in the mouse. Nested expression domains of the genes D1x-2 and Nkx-2.1, plus Pax-g-expressing migrated cells, are characteristic for the mouse subpallium. The genes Pax-6, Tbr-1, and Emx-1 are expressed in the pallium. The pallio-subpallial boundary lies at the interface between the Tbr-1 and D1x-2 expression domains. Differences in the expression topography of Tbr-1 and Emx-1 suggest the existence of a novel ``ventral pallium'' subdivision, which is an Emx-1-negative pallial territory intercalated between the striatum and the lateral pallium. Its derivatives in the mouse belong to the claustroamygdaloid complex. Chicken genes homologous to these mouse genes are expressed in topologically comparable patterns during development. The avian subpallium, called ``paleostriatum,'' shows nested D1x-2 and Nkx-2.1 domains and migrated Pax-6-positive neurons; the avian pallium expresses Pax-6, Tbr-1, and Emx-1 and also contains a distinct Emx-1-negative ventral pallium, formed by the massive domain confusingly called ``neostriatum.'' These expression patterns extend into the septum and the archistriatum, as they do into the mouse septum and amygdala, suggesting that the concepts of pallium and subpallium can be extended to these areas. The similarity of such molecular profiles in the mouse and chicken pallium and subpallium points to common sets of causal determinants. These may underlie similar histogenetic specification processes and field homologies, including some comparable connectivity patterns. (C) 2000 Wiley-Liss, Inc.
    BibTeX:
    @article{Puelles2000,
      author = {Puelles, L and Kuwana, E and Puelles, E and Bulfone, A and Shimamura, K and Keleher, J and Smiga, S and Rubenstein, JLR},
      title = {Pallial and subpallial derivatives in the embryonic chick and mouse telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6, and Tbr-1},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {2000},
      volume = {424},
      number = {3},
      pages = {409-438}
    }
    
    de Quervain, D., Roozendaal, B., Nitsch, R., McGaugh, J. & Hock, C. Acute cortisone administration impairs retrieval of long-term declarative memory in humans {2000} NATURE NEUROSCIENCE
    Vol. {3}({4}), pp. {313-314} 
    article  
    BibTeX:
    @article{Quervain2000,
      author = {de Quervain, DJF and Roozendaal, B and Nitsch, RM and McGaugh, JL and Hock, C},
      title = {Acute cortisone administration impairs retrieval of long-term declarative memory in humans},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {2000},
      volume = {3},
      number = {4},
      pages = {313-314}
    }
    
    Quirk, G., Likhtik, E., Pelletier, J. & Pare, D. Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons {2003} JOURNAL OF NEUROSCIENCE
    Vol. {23}({25}), pp. {8800-8807} 
    article  
    Abstract: In extinction of auditory fear conditioning, rats learn that a tone no longer predicts the occurrence of a footshock. Recent lesion and unit recording studies suggest that the medial prefrontal cortex (mPFC) plays an essential role in the inhibition of conditioned fear following extinction. mPFC has robust projections to the amygdala, a structure that is known to mediate the acquisition and expression of conditioned fear. Fear conditioning potentiates the tone responses of neurons in the basolateral amygdala (BLA), which excite neurons in the central nucleus (Ce) of the amygdala. In turn, the Ce projects to the brainstem and hypothalamic areas that mediate fear responses. The present study was undertaken to test the hypothesis that the mPFC inhibits conditioned fear via feed forward inhibition of Ce output neurons. Recording extracellularly from physiologically identified brainstem-projecting Ce neurons, we tested the effect of mPFC prestimulation on Ce responsiveness to synaptic input. In support of our hypothesis, mPFC prestimulation dramatically reduced the responsiveness of Ce output neurons to inputs from the insular cortex and BLA. Thus, our findings support the idea that mPFC gates impulse transmission from the BLA to Ce, perhaps through GABAergic intercalated cells, thereby gating the expression of conditioned fear.
    BibTeX:
    @article{Quirk2003,
      author = {Quirk, GJ and Likhtik, E and Pelletier, JG and Pare, D},
      title = {Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2003},
      volume = {23},
      number = {25},
      pages = {8800-8807}
    }
    
    QUIRK, G., REPA, J. & LEDOUX, J. FEAR CONDITIONING ENHANCES SHORT-LATENCY AUDITORY RESPONSES OF LATERAL AMYGDALA NEURONS - PARALLEL RECORDINGS IN THE FREELY BEHAVING RAT {1995} NEURON
    Vol. {15}({5}), pp. {1029-1039} 
    article  
    Abstract: The lateral nucleus of the amygdala (LA) is the first site in the amygdala where the plasticity underlying fear conditioning could occur. We simultaneously recorded from multiple LA neurons in freely moving rats during fear conditioning trials in which tones were paired with foot shocks. Conditioning significantly increased the magnitude of tone-elicited responses (often within the first several trials), converted unresponsive cells into tone-responsive ones, and altered functional couplings between LA neurons. The effects of conditioning were greatest on the shortest latency (less than 15 ms) components of the tone-elicited responses, consistent with the hypothesis that direct projections from the auditory thalamus to LA are an important link in the circuitry through which rapid behavioral responses are controlled in the presence of conditioned fear stimuli.
    BibTeX:
    @article{QUIRK1995,
      author = {QUIRK, GJ and REPA, JC and LEDOUX, JE},
      title = {FEAR CONDITIONING ENHANCES SHORT-LATENCY AUDITORY RESPONSES OF LATERAL AMYGDALA NEURONS - PARALLEL RECORDINGS IN THE FREELY BEHAVING RAT},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {1995},
      volume = {15},
      number = {5},
      pages = {1029-1039}
    }
    
    Quirk, G., Russo, G., Barron, J. & Lebron, K. The role of ventromedial prefrontal cortex in the recovery of extinguished fear {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({16}), pp. {6225-6231} 
    article  
    Abstract: Conditioned fear responses to a tone paired with footshock extinguish when the tone is presented repeatedly in the absence of shock. Rather than erase the tone-shock association, extinction is thought to involve new learning accompanied by inhibition of conditioned responding. Despite much interest in extinction from a clinical perspective, little is known about the neural circuits that are involved. Although the prefrontal cortex has a well established role in the inhibition of inappropriate behaviors, previous reports have disagreed as to the role of the ventromedial prefrontal cortex (vmPFC) in extinction. We have reexamined the effects of electrolytic vmPFC lesions made before training on the acquisition, extinction, and recovery of conditioned fear responses in a 2 d experiment. On Day 1 vmPFC lesions had no effect on acquisition or extinction of conditioned freezing and suppression of bar pressing. On Day 2 sham rats recovered only 27% of their acquired freezing, whereas vmPFC-lesioned rats recovered 86 which was indistinguishable from a control group that never received extinction. The high recovery in lesioned rats could not be attributed to decreased motivation or altered sensitivity to footshock. vmPFC lesions that spared the caudal infralimbic (IL) nucleus had no effect. Thus, the vmPFC (particularly the IL nucleus) is not necessary for expression of extinction, but it is necessary for the recall of extinction learning after a long delay. These data suggest a role of the vmPFC in consolidation of extinction learning or the recall of contexts in which extinction took place.
    BibTeX:
    @article{Quirk2000,
      author = {Quirk, GJ and Russo, GK and Barron, JL and Lebron, K},
      title = {The role of ventromedial prefrontal cortex in the recovery of extinguished fear},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {16},
      pages = {6225-6231}
    }
    
    Quiroga, R., Reddy, L., Kreiman, G., Koch, C. & Fried, I. Invariant visual representation by single neurons in the human brain {2005} NATURE
    Vol. {435}({7045}), pp. {1102-1107} 
    article DOI  
    Abstract: It takes a fraction of a second to recognize a person or an object even when seen under strikingly different conditions. How such a robust, high-level representation is achieved by neurons in the human brain is still unclear(1-6). In monkeys, neurons in the upper stages of the ventral visual pathway respond to complex images such as faces and objects and show some degree of invariance to metric properties such as the stimulus size, position and viewing angle(2,4,7-12). We have previously shown that neurons in the human medial temporal lobe (MTL) fire selectively to images of faces, animals, objects or scenes(13,14). Here we report on a remarkable subset of MTL neurons that are selectively activated by strikingly different pictures of given individuals, landmarks or objects and in some cases even by letter strings with their names. These results suggest an invariant, sparse and explicit code, which might be important in the transformation of complex visual percepts into long-term and more abstract memories.
    BibTeX:
    @article{Quiroga2005,
      author = {Quiroga, RQ and Reddy, L and Kreiman, G and Koch, C and Fried, I},
      title = {Invariant visual representation by single neurons in the human brain},
      journal = {NATURE},
      publisher = {NATURE PUBLISHING GROUP},
      year = {2005},
      volume = {435},
      number = {7045},
      pages = {1102-1107},
      doi = {{10.1038/nature03687}}
    }
    
    RASSNICK, S., HEINRICHS, S., BRITTON, K. & KOOB, G. MICROINJECTION OF A CORTICOTROPIN-RELEASING FACTOR ANTAGONIST INTO THE CENTRAL NUCLEUS OF THE AMYGDALA REVERSES ANXIOGENIC-LIKE EFFECTS OF ETHANOL WITHDRAWAL {1993} BRAIN RESEARCH
    Vol. {605}({1}), pp. {25-32} 
    article  
    Abstract: Previous studies have shown that spontaneous exploration of the Elevated Plus Maze provides a sensitive measure of `anxiety' induced by pharmacological or behavioral stressors. In particular, the percent time spent exploring the open arms of the plus maze is decreased during ethanol withdrawal, and this effect is antagonized by intracerebroventricular administration of 25 mug of alpha-helical CRF, a corticotropin-releasing factor antagonist (H.A. Baldwin et al., Psychopharmacology, 103 (1991) 227-232). The present study was designed to examine the effect of alpha-helical CRF infusion within the central nucleus of the amygdala during ethanol withdrawal. Rats were made dependent on ethanol by maintenance on an ethanol-containing liquid diet for 16 days, withdrawn from ethanol and tested on the elevated plus maze at 8 h post-ethanol access. In comparison with pair-fed control rats, ethanol withdrawn subjects spent significantly less percent time exploring the open arms of the plus maze. This decrease in open arm exploration was antagonized by administration of alpha-helical CRF (250 ng) bilaterally into the central nucleus of the amygdala, but not by intracerebroventricular administration of 250 ng of alpha-helical CRF. The ability of intra-amygdala alpha-helical CRF to antagonize decreased open arm exploration is unlikely to be due to changes in motor activity, since general activity on the maze was reduced in all EtOH withdrawal groups. These results suggest that the central nucleus of the amygdala may be an effective site for endogenous CRF systems to mediate anxious behavior associated with ethanol withdrawal.
    BibTeX:
    @article{RASSNICK1993,
      author = {RASSNICK, S and HEINRICHS, SC and BRITTON, KT and KOOB, GF},
      title = {MICROINJECTION OF A CORTICOTROPIN-RELEASING FACTOR ANTAGONIST INTO THE CENTRAL NUCLEUS OF THE AMYGDALA REVERSES ANXIOGENIC-LIKE EFFECTS OF ETHANOL WITHDRAWAL},
      journal = {BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1993},
      volume = {605},
      number = {1},
      pages = {25-32}
    }
    
    Rauch, S., Whalen, P., Shin, L., McInerney, S., Macklin, M., Lasko, N., Orr, S. & Pitman, R. Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: A functional MRI study {2000} BIOLOGICAL PSYCHIATRY
    Vol. {47}({9}), pp. {769-776} 
    article  
    Abstract: Background: Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). We previously developed a method for measuring automatic amygdala responses to general threat-related stimuli; in conjunction with functional magnetic resonance imaging, we used a passive viewing task involving masked presentations of human facial stimuli. Methods: We applied this method to study veterans with PTSD and a comparison cohort of combat-exposed veterans without PTSD. Results: The findings indicate that patients with PTSD exhibit exaggerated amygdala responses to masked-fearful versus masked-happy faces. Conclusions: Although some previous neuroimaging studies of PTSD have demonstrated amygdala recruitment in response to reminders of traumatic events, this represents the first evidence for exaggerated amygdala responses to general negative stimuli in PTSD. Furthermore, by using a probe that emphasizes automaticity, we provide initial evidence of amygdala hyperresponsivity dissociated from the ``top-down `` influences of medial frontal cortex. Biol Psychiatry 2000;47:769-776 (C) 2000 Society of Biological Psychiatry.
    BibTeX:
    @article{Rauch2000,
      author = {Rauch, SL and Whalen, PJ and Shin, LM and McInerney, SC and Macklin, ML and Lasko, NB and Orr, SP and Pitman, RK},
      title = {Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: A functional MRI study},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2000},
      volume = {47},
      number = {9},
      pages = {769-776}
    }
    
    Reiman, E., Lane, R., Ahern, G., Schwartz, G., Davidson, R., Friston, K., Yun, L. & Chen, K. Neuroanatomical correlates of externally and internally generated human emotion {1997} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {154}({7}), pp. {918-925} 
    article  
    Abstract: Objective: Positron emission tomography was used to investigate the neural substrates of normal human emotion and their dependence on the type of emotional stimulus. Method: Twelve healthy female subjects underwent 12 measurements of regional brain activity following the intravenous bolus administration of [O-15]H2O as they alternated between emotion-generating and control film and recall tasks. Automated image analysis techniques were used to characterize and compare the increases in regional brain activity associated with the emotional response to complex visual (film) and cognitive (recall) stimuli. Results: Film- and recall-generated emotion were each associated with significantly increased activity in the vicinity of the medial prefrontal cortex and thalamus, suggesting that these regions participate in aspects of emotion that no not depend on the nature of the emotional stimulus. Film-generated emotion was associated with significantly greater increases in activity bilaterally in the occipitotemporoparietal cortex, lateral cerebellum, hypothalamus, and a region that includes the anterior temporal cortex, amygdala, and hippocampal formation, suggesting that these regions participate in the emotional response to certain exteroceptive sensory stimuli. Recall-generated sadness was associated with significantly greater increases in activity in the vicinity of the anterior insular cortex, suggesting that this region participates iir the emotional response to potentially distressing cognitive or interoceptive sensory stimuli. Conclusions: While this study should be considered preliminary it identified brain regions that participate in externally and internally generated human emotion.
    BibTeX:
    @article{Reiman1997,
      author = {Reiman, EM and Lane, RD and Ahern, GL and Schwartz, GE and Davidson, RJ and Friston, KJ and Yun, LS and Chen, KW},
      title = {Neuroanatomical correlates of externally and internally generated human emotion},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      publisher = {AMER PSYCHIATRIC ASSOCIATION},
      year = {1997},
      volume = {154},
      number = {7},
      pages = {918-925},
      note = {52nd Annual Meeting of the American-Psychosomatic-Society, BOSTON, MA, APR 13-16, 1994}
    }
    
    Reiner, A., Perkel, D., Bruce, L., Butler, A., Csillag, A., Kuenzel, W., Medina, L., Paxinos, G., Shimizu, T., Striedter, G., Wild, M., Ball, G., Durand, S., Gunturkun, O., Lee, D., Mello, C., Powers, A., White, S., Hough, G., Kubikova, L., Smulders, T., Wada, K., Dugas-Ford, J., Husband, S., Yamamoto, K., Yu, J., Siang, C. & Jarvis, E. Revised nomenclature for avian telencephalon and some related brainstem nuclei {2004} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {473}({3}), pp. {377-414} 
    article DOI  
    Abstract: The standard nomenclature that has been used for many telencephalic and related brainstem structures in birds is based on flawed assumptions of homology to mammals. In particular, the outdated terminology implies that most of the avian telencephalon is a hypertrophied basal ganglia, when it is now clear that most of the avian telencephalon is neurochemically, hodologically, and functionally comparable to the mammalian neocortex, claustrum, and pallial amygdala (all of which derive from the pallial sector of the developing telencephalon). Recognizing that this promotes misunderstanding of the functional organization of avian brains and their evolutionary relationship to mammalian brains, avian brain specialists began discussions to rectify this problem, culminating in the Avian Brain Nomenclature Forum held at Duke University in July 2002, which approved a new terminology for avian telencephalon and some allied brainstem cell groups. Details of this new terminology are presented here, as is a rationale for each name change and evidence for any homologies implied by the new names. Revisions for the brainstem focused on vocal control, catecholaminergic, cholinergic, and basal ganglia-related nuclei. For example, the Forum recognized that the hypoglossal nucleus had been incorrectly identified as the nucleus intermedius in the Karten and Hodos (1967) pigeon brain atlas, and what was identified as the hypoglossal nucleus in that atlas should instead be called the supraspinal nucleus. The locus ceruleus of this and other avian atlases was noted to consist of a caudal noradrenergic part homologous to the mammalian locus coeruleus and a rostral region corresponding to the mammalian A8 dopaminergic cell group. The midbrain dopaminergic cell group in birds known as the nucleus tegmenti pedunculo-pontinus pars compacta was recognized as homologous to the mammalian substantia nigra pars compacta and was renamed accordingly; a group of gamma-aminobutyric acid (GABA)ergic neurons at the lateral edge of this region was identified as homologous to the mammalian substantia nigra pars reticulata and was also renamed accordingly. A field of cholinergic neurons in the rostral avian hindbrain was named the nucleus pedunculopontinus tegmenti, whereas the anterior nucleus of the ansa lenticularis in the avian diencephalon was renamed the subthalamic nucleus, both for their evident mammalian homologues. For the basal (i.e., subpallial) telencephalon, the actual parts of the basal ganglia were given names reflecting their now evident homologues. For example, the lobus parolfactorius and paleostriatum augmentatum were acknowledged to make up the dorsal subdivision of the striatal part of the basal ganglia and were renamed as the medial and lateral striatum. The paleostriaturn primitivum was recognized as homologous to the mammalian globus pallidus and renamed as such. Additionally, the rostroventral part of what was called the lobus parolfactorius was acknowledged as comparable to the mammalian nucleus accumbens, which, together with the olfactory tubercle, was noted to be part of the ventral striatum in birds. A ventral pallidum, a basal cholinergic cell group, and medial and lateral bed nuclei of the stria terminalis were also recognized. The dorsal (i.e., pallial) telencephalic regions that had been erroneously named to reflect presumed homology to striatal parts of mammalian basal ganglia were renamed as part of the pallium, using prefixes that retain most established abbreviations, to maintain continuity with the outdated nomenclature. We concluded, however, that one-to-one (i.e., discrete) homologies with mammals are still uncertain for most of the telencephalic pallium in birds and thus the new pallial terminology is largely devoid of assumptions of one-to-one homologies with mammals. The sectors of the hyperstriatum composing the Wulst (i.e., the hyperstyiatum accessorium intermedium, and dorsale), the hyperstriatum ventrale, the neostriatum, and the archistriatum have been renamed (respectively) the hyperpallium (hypertrophied pallium), the mesopallium (middle pallium), the nidopallium (nest pallium), and the arcopallium (arched pallium). The posterior part of the archistriatum has been renamed the posterior pallial amygdala, the nucleus taeniae recognized as part of the avian amygdala, and a region inferior to the posterior paleostriaturn primitivum included as a subpallial part of the avian amygdala. The names of some of the laminae and fiber tracts were also changed to reflect current understanding of the location of pallial and subpallial sectors of the avian telencephalon. Notably, the lamina medularis dorsalis has been renamed the pallial-subpallial lamina. We urge all to use this new terminology, because we believe it will promote better communication among neuroscientists. (C) 2004 Wiley-Liss, Inc.
    BibTeX:
    @article{Reiner2004,
      author = {Reiner, A and Perkel, DJ and Bruce, LL and Butler, AB and Csillag, A and Kuenzel, W and Medina, L and Paxinos, G and Shimizu, T and Striedter, G and Wild, M and Ball, GF and Durand, S and Gunturkun, O and Lee, DW and Mello, CV and Powers, A and White, SA and Hough, G and Kubikova, L and Smulders, TV and Wada, K and Dugas-Ford, J and Husband, S and Yamamoto, K and Yu, J and Siang, C and Jarvis, ED},
      title = {Revised nomenclature for avian telencephalon and some related brainstem nuclei},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {2004},
      volume = {473},
      number = {3},
      pages = {377-414},
      doi = {{10.1002/cne.20118}}
    }
    
    RESIBOIS, A. & ROGERS, J. CALRETININ IN RAT-BRAIN - AN IMMUNOHISTOCHEMICAL STUDY {1992} NEUROSCIENCE
    Vol. {46}({1}), pp. {101-134} 
    article  
    Abstract: Calretinin is a calcium-binding protein related to calbindin-D28k; both are present in different though overlapping sets of neurons in brains of birds and mammals. We describe in detail the pattern of calretinin immunoreactivity in the rat brain. As in chick brain, calretinin immunoreactivity is abundant in various sensory pathways (particularly certain cells and fibres of the cochlear nuclei and olfactory bulb), in the heterogeneous parts of the brainstem and in parts of the hypothalamus. Many primary sensory fibres are strongly positive. Major groups of calretinin-positive neurons also include the thalamic reticular nucleus, triangular septal nucleus, lateral mammillary nucleus and substantia nigra pars compacta. Many other calretinin-positive cells are recognizable as local inhibitory neurons. Calretinin is absent from all but a few cells in the cerebral cortex, and is never found in motor neurons. There are also some distinctive positive structures whose identity is uncertain, notably irregular ``shells'' of cells and fibres around the thalamus and in the amygdala and an unnamed cell type in the vestibulocerebellum.
    BibTeX:
    @article{RESIBOIS1992,
      author = {RESIBOIS, A and ROGERS, JH},
      title = {CALRETININ IN RAT-BRAIN - AN IMMUNOHISTOCHEMICAL STUDY},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1992},
      volume = {46},
      number = {1},
      pages = {101-134}
    }
    
    Ressler, K. & Nemeroff, C. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders {2000} DEPRESSION AND ANXIETY
    Vol. {12}({Suppl. 1}), pp. {2-19} 
    article  
    Abstract: There is abundant evidence for abnormalities of the norepinephrine (NE) and serotonin (5HT) neurotransmitter systems in depression and anxiety disorders. The majority of evidence supports underactivation of serotonergic function and complex dysregulation of noradrenergic function, most consistent with overactivation of this system. Treatment for these disorders requires perturbation of these systems. Reproducible increases in serotonergic function and decreases in noradrenergic function accompany treatment with antidepressants, and these alterations may be necessary for antidepressant efficacy. Dysregulation of these systems clearly mediates many symptoms of depression and anxiety. The underlying causes of these disorders, however, are less likely to be found within the NE and 5HT systems, per se. Rather their dysfunction is likely due to their role in modulating, and being modulated by, other neurobiologic systems that together mediate the symptoms of affective illness. Clarification of noradrenergic and serotonergic modulation of various brain regions may yield a greater understanding of specific symptomatology, as well as the underlying circuitry involved in euthymic and abnormal mood and anxiety states. Disrupted cortical regulation may mediate impaired concentration and memory, together with uncontrollable worry. Hypothalamic abnormalities likely contribute to altered appetite, libido, and autonomic symptoms. Thalamic and brainstem dysregulation contributes to altered sleep and arousal states. Finally, abnormal modulation of cortical-hippocampal-amygdala pathways may contribute to chronically hypersensitive stress and fear responses, possibly mediating features of anxiety, anhedonia, aggression, and affective dyscontrol. The continued appreciation of the neural circuitry mediating affective states and their modulation by neurotransmitter systems should further the understanding of the pathophysiology of affective and anxiety disorders. (C) 2000 Wiley-Liss, Inc.
    BibTeX:
    @article{Ressler2000,
      author = {Ressler, KJ and Nemeroff, CB},
      title = {Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders},
      journal = {DEPRESSION AND ANXIETY},
      publisher = {WILEY-LISS},
      year = {2000},
      volume = {12},
      number = {Suppl. 1},
      pages = {2-19}
    }
    
    REYNOLDS, G. INCREASED CONCENTRATIONS AND LATERAL ASYMMETRY OF AMYGDALA DOPAMINE IN SCHIZOPHRENIA {1983} NATURE
    Vol. {305}({5934}), pp. {527-529} 
    article  
    BibTeX:
    @article{REYNOLDS1983,
      author = {REYNOLDS, GP},
      title = {INCREASED CONCENTRATIONS AND LATERAL ASYMMETRY OF AMYGDALA DOPAMINE IN SCHIZOPHRENIA},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1983},
      volume = {305},
      number = {5934},
      pages = {527-529}
    }
    
    RICARDO, J. & KOH, E. ANATOMICAL EVIDENCE OF DIRECT PROJECTIONS FROM NUCLEUS OF SOLITARY TRACT TO HYPOTHALAMUS, AMYGDALA, AND OTHER FOREBRAIN STRUCTURES IN RAT {1978} BRAIN RESEARCH
    Vol. {153}({1}), pp. {1-26} 
    article  
    BibTeX:
    @article{RICARDO1978,
      author = {RICARDO, JA and KOH, ET},
      title = {ANATOMICAL EVIDENCE OF DIRECT PROJECTIONS FROM NUCLEUS OF SOLITARY TRACT TO HYPOTHALAMUS, AMYGDALA, AND OTHER FOREBRAIN STRUCTURES IN RAT},
      journal = {BRAIN RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {1978},
      volume = {153},
      number = {1},
      pages = {1-26}
    }
    
    RICHES, I., WILSON, F. & BROWN, M. THE EFFECTS OF VISUAL-STIMULATION AND MEMORY ON NEURONS OF THE HIPPOCAMPAL-FORMATION AND THE NEIGHBORING PARAHIPPOCAMPAL GYRUS AND INFERIOR TEMPORAL CORTEX OF THE PRIMATE {1991} JOURNAL OF NEUROSCIENCE
    Vol. {11}({6}), pp. {1763-1779} 
    article  
    Abstract: The activity of 736 single neurons was recorded from the hippocampal formation (HF), the rhinal cortex (RH), the medial and anterior inferior temporal cortex (TE), or areas TF and TH of the parahippocampal gyrus (PHG) of monkeys during the performance of a delayed matching to sample task. The results indicate differences between the areas in their contributions to sensory processing and memory. Of the neurons, 55% responded to either the first (S1) and/or the second (S2) of the two successively presented visual stimuli. The proportion of responsive neurons and the proportion of neurons that responded selectively on the basis of shape or color (but not size) were significantly higher in areas TE+RH than in HF+PHG. The responses to S1 differed from those to S2 for 18% of the total sample: of these differentially responsive neurons, 66% of the TE+RH neurons responded more strongly to S1 (the sample presentation, allowing stimulus acquisition), whereas 71% of the HF+PHG neurons responded more strongly to S2 (the match/non-match comparison, when the behavioral decision could be made). Of 239 TE+RH neurons recorded during the delayed matching task or when objects were shown, 12% displayed evidence of memory for the previous occurrence of stimuli by responding strongly to the first, but significantly less strongly to subsequent presentations of visual stimuli that were novel or had not been seen recently. In contrast, none (0 of 328 neurons so tested in HF and PHG had a response that declined significantly on stimulus repetition. For six (86 of seven TE+RH neurons tested, the decrement in response persisted even after distraction by intervening presentations of other stimuli. Further evidence of information storage was found for 7 (33 of 21 neurons for which responses to the first presentations of unfamiliar objects were significantly greater than to the first presentations of very familiar objects, even though the familiar objects had not been seen for > 15 min.
    BibTeX:
    @article{RICHES1991,
      author = {RICHES, IP and WILSON, FAW and BROWN, MW},
      title = {THE EFFECTS OF VISUAL-STIMULATION AND MEMORY ON NEURONS OF THE HIPPOCAMPAL-FORMATION AND THE NEIGHBORING PARAHIPPOCAMPAL GYRUS AND INFERIOR TEMPORAL CORTEX OF THE PRIMATE},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {OXFORD UNIV PRESS INC},
      year = {1991},
      volume = {11},
      number = {6},
      pages = {1763-1779}
    }
    
    RIZVI, T., ENNIS, M., BEHBEHANI, M. & SHIPLEY, M. CONNECTIONS BETWEEN THE CENTRAL NUCLEUS OF THE AMYGDALA AND THE MIDBRAIN PERIAQUEDUCTAL GRAY - TOPOGRAPHY AND RECIPROCITY {1991} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {303}({1}), pp. {121-131} 
    article  
    Abstract: Previous reports indicate that the midbrain periaqueductal gray and the central nucleus of the amygdala are interconnected but the organization of these projections has not been characterized. We have analyzed this reciprocal circuitry using anterograde and retrograde tracing methods and image analysis. OUr findings reveal that innervation of periaqueductal gray from the central nucleus of the amygdala is extensive and discretely organized along the rostrocaudal axis of periaqueductal gray. In addition, the reciprocal projection from periaqueductal gray to the central nucleus of the amygdala is more extensive and more highly organized than previously suggested. Multiple or single discrete injections of wheatgerm agglutinin-horseradish peroxidase into several rostrocaudal levels of periaqueductal gray retrogradely labeled a substantial population of neurons, predominantly located in the medial division of the central nucleus of the amygdala. Tracer injections into the central nucleus revealed a high degree of spatial organization in the projection from this nucleus to periaqueductal gray. Two discrete longitudinally directed columns in dorsomedial and lateral/ventrolateral periaqueductal gray are heavily targeted by central amygdalar inputs throughout the rostral one-half to two-thirds of periaqueductal gray. Beginning at the level of dorsal raphe and continuing caudally, inputs from the central nucleus terminate more uniformly throughout the ventral half of periaqueductal gray. In addition, a substantial population of periaqueductal gray neurons were retrogradely labeled from the central nucleus of the amygdala; these were heterogeneously distributed along the rostrocaudal axis of periaqueductal gray, and included both raphe and non-raphe neurons. Thus, the present study demonstrates that periaqueductal gray receives heavy, highly organized projections from the central nucleus of the amygdala and, in turn, has reciprocal connections with the central nucleus. Previous studies have demonstrated that longitudinally organized columns of output neurons located in dorsomedial and lateral/ventrolateral periaqueductal gray project to the ventral medulla. Thus, there may be considerable overlap between the two longitudinally organized terminal input columns from the central nucleus of the amygdala and the two longitudinal columns of descending projection neurons from periaqueductal gray to the ventral medulla. The central nucleus the of amygdala has been implicated in a variety of emotional/cognitive functions ranging from fear and orienting responses, defensive and aversive reactions, associative conditioning, cardiovascular regulation, and antinociception. Many of these same functions are strongly represented in the periaqueductal gray. It is noteworthy that the present results demonstrate that lateral periaqueductal gray, a preeminent central trigger site for behavioral and autonomic components of the defense/aversion response, is heavily targeted by inputs from the central nucleus of the amygdala at all levels of periaqueductal gray. thus, the central nucleus of the amygdala to periaqueductal gray projection may be involved in the neural integration of behavioral, antinociceptive and autonomic responses with emotional state. In addition, the present demonstration of extensive reciprocal connections between the central nucleus of the amygdala and periaqueductal gray represents a route via which functional activity represented in periaqueductal gray may gain access to a forebrain structure long implicated in the integration of the cognitive and autonomic components of emotional behavior. Thus, the periaqueductal gray to central nucleus of the amygdala projection may provide a relatively direct linkage between critical species-preserving behavioral reactions and a forebrain structure capable of influencing multiple nodal points in the descending autonomic system.
    BibTeX:
    @article{RIZVI1991,
      author = {RIZVI, TA and ENNIS, M and BEHBEHANI, MM and SHIPLEY, MT},
      title = {CONNECTIONS BETWEEN THE CENTRAL NUCLEUS OF THE AMYGDALA AND THE MIDBRAIN PERIAQUEDUCTAL GRAY - TOPOGRAPHY AND RECIPROCITY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1991},
      volume = {303},
      number = {1},
      pages = {121-131}
    }
    
    RODRIGO, J., SPRINGALL, D., UTTENTHAL, O., BENTURA, M., ABADIAMOLINA, F., RIVEROSMORENO, V., MARTINEZMURILLO, R., POLAK, J. & MONCADA, S. LOCALIZATION OF NITRIC-OXIDE SYNTHASE IN THE ADULT-RAT BRAIN {1994} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {345}({1312}), pp. {175-221} 
    article  
    Abstract: The distribution of the immunoreactivity to nitric oxide synthase has been examined from rostral to caudal areas of the rat central nervous system using light microscopy. Endogenous nitric oxide synthase was located using a specific polyclonal antiserum, produced against affinity purified nitric oxide synthase from whole rat brain, following the avidin-biotin peroxidase procedure. Immunoreactive cell bodies and processes showed a widespread distribution in the brain. In the telencephalon, immunoreactive structures were distributed in all areas of the cerebral cortex, the ventral endopiriform nucleus and claustrum, the main and accessory olfactory bulb, the anterior and posterior olfactory nuclei, the precommisural hippocampus, the taenia tecta, the nucleus accumbens, the stria terminalis, the caudate putamen, the olfactory tubercle and islands of Calleja, septum, globus pallidus and substantia innominata, hippocampus and amygdala. In the diencephalon, the immunoreactivity was largely found in both the hypothalamus and thalamus. In the hypothalamus, immunoreactive cell bodies were characteristically located in the perivascular-neurosecretory systems and mamillary bodies. In addition, immunoreactive nerve fibres were detected in the median eminence of the infundibular stem. The mesencephalon showed nitric oxide synthase immunoreactivity in the ventral tegmental area, the interpeduncular nucleus, the rostral linear nucleus of the raphe and the dorsal raphe nucleus. Immunoreactive structures were also found in the nuclei of the central grey, the peripeduncular nucleus and substantia nigra pars lateralis, the geniculate nucleus and in the superior and inferior colliculi. The pens displayed immunoreactive structures principally in the pedunculopontine and laterodorsal tegmental nuclei, the ventral tegmental nucleus, the reticulotegmental pontine nucleus, the parabrachial nucleus and locus coeruleus. In the medulla oblongata, immunoreactive neurons and processes were detected in the principal sensory trigeminal nucleus, the trapezoid body, the raphe magnus, the pontine reticular nuclei, the supragenual nucleus, the prepositus hypoglossal nucleus, the medial and spinal vestibular nuclei, the dorsal cochlear nucleus, the medullary reticular field, the nucleus of the solitary tract, the gracile and cuneate nuclei, the dorsal nucleus of the vagus nerve and the oral, interpolar and caudal parts of the spinal trigeminal nucleus. In the cerebellum, the stellate and basket cells showed immunoreactivity, which was also seen in the basket terminal fibres of the Purkinje cell layer. Isolated immunoreactive Purkinje cells were found in the vermis and parafloccular regions of the cerebellum. In the granular layer of the cerebellum, the granular cells and glomeruli were also immunoreactive. Numerous positive varicose nerve fibres and occasional neurons were also found in the lateral and interposed cerebellar nuclei. Immunoreactive processes were found close to and penetrating the ependymal cells of the ventricular walls, particularly the lateral ventricles. Immunoreactive cell bodies were also detected in the circumventricular organs, including the subfornical organ and area postrema. Cerebral blood vessels were largely surrounded by varicose immunoreactive neuronal processes forming dense networks. Our demonstration of the widespread distribution of the enzyme nitric oxide synthase in diverse nuclei of the rat brain generally confirms earlier histochemical studies and suggests that this enzyme may affect the function of various neurotransmitter-specific systems. The possible implication of nitric oxide synthase in the regulation of the cerebrospinal fluid system and of cerebral blood circulation is discussed.
    BibTeX:
    @article{RODRIGO1994,
      author = {RODRIGO, J and SPRINGALL, DR and UTTENTHAL, O and BENTURA, ML and ABADIAMOLINA, F and RIVEROSMORENO, V and MARTINEZMURILLO, R and POLAK, JM and MONCADA, S},
      title = {LOCALIZATION OF NITRIC-OXIDE SYNTHASE IN THE ADULT-RAT BRAIN},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      publisher = {ROYAL SOC LONDON},
      year = {1994},
      volume = {345},
      number = {1312},
      pages = {175-221}
    }
    
    Rogan, M., Staubli, U. & LeDoux, J. Fear conditioning induces associative long-term potentiation in the amygdala {1997} NATURE
    Vol. {390}({6660}), pp. {604-607} 
    article  
    Abstract: Long-term potentiation (LTP) is an experience-dependent form of neural plasticity believed to involve mechanisms that underlie memory formation(1-3). Lip has been studied most extensively in the hippocampus, but the relation between hippocampal Lip and memory has been difficult to establish(4-6). Here we explore the relation between LTP and memory in fear conditioning, an amygdala-dependent form of learning in which an innocuous conditioned stimulus (CS) elicits fear responses after being associatively paired with an aversive unconditioned stimulus (US). We have previously shown that Lip induction in pathways that transmit auditory CS information to the lateral nucleus of the amygdala (LA) increases auditory-evoked field potentials in this nucleus(7). Now we show that fear conditioning alters auditory CS-evoked responses in LA in the same way as Lip induction, The changes parallel the acquisition of CS-elicited fear behaviour, are enduring, and do not occur if the CS and US remain unpaired. LTP-like associative processes thus occur during fear conditioning, and these may underlie the long-term associative plasticity that constitutes memory of the conditioning experience.
    BibTeX:
    @article{Rogan1997,
      author = {Rogan, MT and Staubli, UV and LeDoux, JE},
      title = {Fear conditioning induces associative long-term potentiation in the amygdala},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1997},
      volume = {390},
      number = {6660},
      pages = {604-607}
    }
    
    ROLLS, E. NEUROPHYSIOLOGICAL MECHANISMS UNDERLYING FACE PROCESSING WITHIN AND BEYOND THE TEMPORAL CORTICAL VISUAL AREAS {1992} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {335}({1273}), pp. {11-21} 
    article  
    Abstract: The ways in which information about faces is represented and stored in the temporal lobe visual areas of primates, as shown by recordings from single neurons in macaques, are considered. Some neurons that respond primarily to faces are found in the cortex in the anterior part of the superior temporal sulcus in which neurons are especially likely to be tuned to facial expression and to face movement involved in gesture), and in the TE areas more ventrally forming the inferior temporal gyrus in which neurons are more likely to have responses related to the identity of faces). Quantitative studies of the responses of the neurons that respond differently to the faces of different individuals show that information about the identity of the individual is represented by the responses of a population of neurons, that is, ensemble encoding rather than `grandmother cell' encoding is used. It is argued that this type of tuning is a delicate compromise between very fine tuning, which has the advantage of low interference in neuronal network operations but the disadvantage of losing the useful properties (such as generalization, completion and graceful degradation) of storage in neuronal networks, and broad tuning, which has the advantage of allowing these properties of neuronal networks to be realized but the disadvantage of leading to interference between the different memories stored in an associative network. There is evidence that the responses of some of these neurons are altered by experience so that new stimuli become incorporated in the network. It is shown that the representation that is built in temporal cortical areas shows considerable invariance for size, contrast, spatial frequency and translation. Thus the representation is in a form which is particularly useful for storage and as an output from the visual system. It is also shown that one of the representations that is built is object based, which is suitable for recognition and as an input to associative memory, and that another is viewer centred, which is appropriate for conveying information about gesture. Ways are considered in which such cortical representations might be built by competitive self-organization aided by backprojections in the multistage cortical processing hierarchy which has convergence from stage to stage.
    BibTeX:
    @article{ROLLS1992,
      author = {ROLLS, ET},
      title = {NEUROPHYSIOLOGICAL MECHANISMS UNDERLYING FACE PROCESSING WITHIN AND BEYOND THE TEMPORAL CORTICAL VISUAL AREAS},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      publisher = {ROYAL SOC LONDON},
      year = {1992},
      volume = {335},
      number = {1273},
      pages = {11-21}
    }
    
    Roozendaal, B. Stress and memory: Opposing effects of glucocorticoids on memory consolidation and memory retrieval {2002} NEUROBIOLOGY OF LEARNING AND MEMORY
    Vol. {78}({3}), pp. {578-595} 
    article DOI  
    Abstract: It is well established that glucocorticoid hormones, secreted by the adrenal cortex after a stressful event, influence cognitive performance. Some studies have found glucocorticoid-induced memory enhancement. However, many studies have reported impairing effects of glucocorticoids on memory function. This paper reviews recent findings from this laboratory on the acute effects of glucocorticoids in rats on specific memory phases, i.e., memory consolidation and memory retrieval. The evidence suggests that the consequences of glucocorticoid activation on cognition depend largely on the different memory phases investigated. Posttraining activation of glucocorticoid-sensitive pathways involving glucocorticoid receptors enhances memory consolidation in a pattern highly similar to that previously described for adrenal catecholamines. Also, similar to catecholamine effects on memory consolidation, glucocorticoid influences on memory consolidation depend on noradrenergic activation of the basolateral complex of the amygdala and interactions with other brain regions. By contrast, memory retrieval processes are usually impaired with high circulating levels of glucocorticoids or following infusions of glucocorticoid receptor agonists into the hippocampus. The hypothesis is proposed that these apparently dual effects of glucocorticoids on memory consolidation and memory retrieval might be related and that the basolateral complex of the amygdala is a key structure in a memory-modulatory system that regulates, in concert with other brain regions, stress and glucocorticoid effects on both memory consolidation and memory retrieval. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Roozendaal2002,
      author = {Roozendaal, B},
      title = {Stress and memory: Opposing effects of glucocorticoids on memory consolidation and memory retrieval},
      journal = {NEUROBIOLOGY OF LEARNING AND MEMORY},
      publisher = {ACADEMIC PRESS INC ELSEVIER SCIENCE},
      year = {2002},
      volume = {78},
      number = {3},
      pages = {578-595},
      note = {7th Conference on the Neurobiology of Learning and Memory, IRVINE, CALIFORNIA, NOV 07-09, 2001},
      doi = {{10.1006/nlme.2002.4080}}
    }
    
    Roozendaal, B. 1999 Curt P. Richter Award - Glucocorticoids and the regulation of memory consolidation {2000} PSYCHONEUROENDOCRINOLOGY
    Vol. {25}({3}), pp. {213-238} 
    article  
    Abstract: This paper summarizes recent findings on the amygdala's role in mediating acute effects of glucocorticoids on memory consolidation in rats. Posttraining activation of glucocorticoid-sensitive pathways involving glucocorticoid receptors (GRs or type II) enhances memory consolidation in a dose-dependent inverted-U fashion. Selective lesions of the basolateral nucleus of the amygdala (BLA) or infusions of beta-adrenoceptor antagonists into the BLA block the memory-modulatory effects of systemic injections of glucocorticoids. Additionally, posttraining infusions of a specific GR agonist administered directly into the BLA enhance memory consolidation, whereas those of a GR antagonist impair. These findings indicate that glucocorticoid effects on memory consolidation are mediated, in part, by an activation of GRs in the BLA and that the effects require beta-adrenergic activity in the BLA. Other findings indicate that the BLA interacts with the hippocampus in mediating glucocorticoid-induced modulatory influences on memory consolidation. Lesions of the BLA or inactivation of beta-adrenoceptors within the BLA also block the memory-modulatory effects of intra-hippocampal administration of a GR agonist or antagonist. These findings are in agreement with the general hypothesis that the BLA integrates hormonal and neuromodulatory influences on memory consolidation. However, the BLA is not a permanent locus of storage for this information, but modulates consolidation processes for explicit/associative memories in other brain regions, including the hippocampus. (C) 2000 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Roozendaal2000,
      author = {Roozendaal, B},
      title = {1999 Curt P. Richter Award - Glucocorticoids and the regulation of memory consolidation},
      journal = {PSYCHONEUROENDOCRINOLOGY},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {2000},
      volume = {25},
      number = {3},
      pages = {213-238}
    }
    
    Rosen, H., Gorno-Tempini, M., Goldman, W., Perry, R., Schuff, N., Weiner, M., Feiwell, R., Kramer, J. & Miller, B. Patterns of brain atrophy in frontotemporal dementia and semantic dementia {2002} NEUROLOGY
    Vol. {58}({2}), pp. {198-208} 
    article  
    Abstract: Objective: To identify and compare the patterns of cerebral atrophy associated with two clinical variants of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (FTD) and semantic dementia (SemD). Methods: Twenty patients with FTLD were classified as having FTD (N = 8) or SemD) (N = 12) based on current clinical criteria. Both groups showed a similar spectrum of behavioral abnormalities, as indicated by the neuropsychiatric inventory. T1-weighted MRI was obtained for each patient and 20 control subjects. The regions of focal gray matter tissue loss associated with both FTD and SemD, as well as those differing between the two groups were examined using voxel-based morphometry. Results: Regions of significant atrophy seen in both groups were located in the ventromedial frontal cortex, the posterior orbital frontal regions bilaterally, the insula bilaterally, and the left anterior cingulate cortex. The FTD, but not the SemD, g-roup showed atrophy in the right dorsolateral frontal cortex and the left premotor cortex. The SemD, but not the FTD, group showed tissue loss in the anterior temporal cortex and the amygdala/anterior hippocampal region bilaterally. Conclusions: Although FTD and SemD are associated with different overall patterns of brain atrophy, regions of gray matter tissue loss in the orbital frontal, insular, and anterior cingulate regions are present in both groups. The authors suggest that pathology in the areas of atrophy associated with both FTD and SemD) may underlie some the behavioral symptoms seen in the two disorders.
    BibTeX:
    @article{Rosen2002,
      author = {Rosen, HJ and Gorno-Tempini, ML and Goldman, WP and Perry, RJ and Schuff, N and Weiner, M and Feiwell, R and Kramer, JH and Miller, BL},
      title = {Patterns of brain atrophy in frontotemporal dementia and semantic dementia},
      journal = {NEUROLOGY},
      publisher = {LIPPINCOTT WILLIAMS & WILKINS},
      year = {2002},
      volume = {58},
      number = {2},
      pages = {198-208}
    }
    
    Rosen, J. & Schulkin, J. From normal fear to pathological anxiety {1998} PSYCHOLOGICAL REVIEW
    Vol. {105}({2}), pp. {325-350} 
    article  
    Abstract: In this article the authors address how pathological anxiety may develop from adaptive fear states. Fear responses (e.g., freezing, startle, heart rate and blood pressure changes, and increased vigilance) are functionally adaptive behavioral and perceptual responses elicited during danger to facilitate appropriate defensive responses that can reduce danger or injury (e.g., escape and avoidance). Fear is a central motive state of action tendencies subserved by fear circuits, with the amygdala playing a central role. Pathological anxiety is conceptualized as an exaggerated fear state in which hyperexcitability of fear circuits that include the amygdala and extended amygdala (i.e., bed nucleus of the stria terminalis) is expressed as hypervigilance and increased behavioral responsivity to fearful stimuli. Reduced thresholds for activation and hyperexcitability in fear circuits develop through sensitization-or kindling-like processes that involve neuropeptides, hormones, and other proteins. Hyperexcitability in fear circuits is expressed as pathological anxiety that is manifested in the various anxiety disorders.
    BibTeX:
    @article{Rosen1998,
      author = {Rosen, JB and Schulkin, J},
      title = {From normal fear to pathological anxiety},
      journal = {PSYCHOLOGICAL REVIEW},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1998},
      volume = {105},
      number = {2},
      pages = {325-350}
    }
    
    ROSENE, D. & VANHOESEN, G. HIPPOCAMPAL EFFERENTS REACH WIDESPREAD AREAS OF CEREBRAL-CORTEX AND AMYGDALA IN RHESUS-MONKEY {1977} SCIENCE
    Vol. {198}({4314}), pp. {315-317} 
    article  
    BibTeX:
    @article{ROSENE1977,
      author = {ROSENE, DL and VANHOESEN, GW},
      title = {HIPPOCAMPAL EFFERENTS REACH WIDESPREAD AREAS OF CEREBRAL-CORTEX AND AMYGDALA IN RHESUS-MONKEY},
      journal = {SCIENCE},
      publisher = {AMER ASSOC ADVANCEMENT SCIENCE},
      year = {1977},
      volume = {198},
      number = {4314},
      pages = {315-317}
    }
    
    Rothbart, M., Ahadi, S. & Evans, D. Temperament and personality: Origins and outcomes {2000} JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY
    Vol. {78}({1}), pp. {122-135} 
    article  
    Abstract: This article reviews how a temperament approach emphasizing biological and developmental processes can integrate constructs from subdisciplines of psychology to further the study of personality. Basic measurement strategies and findings in the investigation of temperament in infancy and childhood are reviewed. These include linkage of temperament dimensions with basic affective-motivational and attentional systems, including positive affect/approach, fear, frustration/anger, and effortful control. Contributions of biological models that may support these processes are then reviewed. Research indicating how a temperament approach can lead researchers of social and personality development to investigate important person-environment interactions is also discussed. Lastly, adult research suggesting links between temperament dispositions and the Big Five personality factors is described.
    BibTeX:
    @article{Rothbart2000,
      author = {Rothbart, MK and Ahadi, SA and Evans, DE},
      title = {Temperament and personality: Origins and outcomes},
      journal = {JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {2000},
      volume = {78},
      number = {1},
      pages = {122-135}
    }
    
    Sah, P., Faber, E., De Armentia, M. & Power, J. The amygdaloid complex: Anatomy and physiology {2003} PHYSIOLOGICAL REVIEWS
    Vol. {83}({3}), pp. {803-834} 
    article DOI  
    Abstract: A converging body of literature over the last 50 years has implicated the amygdala in assigning emotional significance or value to sensory information. In particular, the amygdala has been shown to be an essential component of the circuitry underlying fear-related responses. Disorders in the processing of fear-related information are likely to be the underlying cause of some anxiety disorders in humans such as posttraumatic stress. The amygdaloid complex is a group of more than 10 nuclei that are located in the midtemporal lobe. These nuclei can be distinguished both on cytoarchitectonic and connectional grounds. Anatomical tract tracing studies have shown that these nuclei have extensive intranuclear and internuclear connections. The afferent and efferent connections of the amygdala have also been mapped in detail, showing that the amygdaloid complex has extensive connections with cortical and subcortical regions. Analysis of fear conditioning in rats has suggested that long-term synaptic plasticity of inputs to the amygdala underlies the acquisition and perhaps storage of the fear memory. In agreement with this proposal, synaptic plasticity has been demonstrated at synapses in the amygdala in both in vitro and in vivo studies. In this review, we examine the anatomical and physiological substrates proposed to underlie amygdala function.
    BibTeX:
    @article{Sah2003,
      author = {Sah, P and Faber, ESL and De Armentia, ML and Power, J},
      title = {The amygdaloid complex: Anatomy and physiology},
      journal = {PHYSIOLOGICAL REVIEWS},
      publisher = {AMER PHYSIOLOGICAL SOC},
      year = {2003},
      volume = {83},
      number = {3},
      pages = {803-834},
      doi = {{10.1152/physrev.00002.2003}}
    }
    
    Sandberg, R., Yasuda, R., Pankratz, D., Carter, T., Del Rio, J., Wodicka, L., Mayford, M., Lockhart, D. & Barlow, C. Regional and strain-specific gene expression mapping in the adult mouse brain {2000} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {97}({20}), pp. {11038-11043} 
    article  
    Abstract: To determine the genetic causes and molecular mechanisms responsible for neurobehavioral differences in mice, we used highly parallel gene expression profiling to detect genes that are differentially expressed between the 129SvEv and C57BL/6 mouse strains at baseline and in response to seizure. In addition, we identified genes that are differentially expressed in specific brain regions. We found that approximately 1% of expressed genes are differentially expressed between strains in at least one region of the brain and that the gene expression response to seizure is significantly different between the two inbred strains. The results lead to the identification of differences in gene expression that may account for distinct phenotypes in inbred strains and the unique functions of specific brain regions.
    BibTeX:
    @article{Sandberg2000,
      author = {Sandberg, R and Yasuda, R and Pankratz, DG and Carter, TA and Del Rio, JA and Wodicka, L and Mayford, M and Lockhart, DJ and Barlow, C},
      title = {Regional and strain-specific gene expression mapping in the adult mouse brain},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {2000},
      volume = {97},
      number = {20},
      pages = {11038-11043}
    }
    
    SARTER, M. & MARKOWITSCH, H. INVOLVEMENT OF THE AMYGDALA IN LEARNING AND MEMORY - A CRITICAL-REVIEW, WITH EMPHASIS ON ANATOMICAL RELATIONS {1985} BEHAVIORAL NEUROSCIENCE
    Vol. {99}({2}), pp. {342-380} 
    article  
    BibTeX:
    @article{SARTER1985,
      author = {SARTER, M and MARKOWITSCH, HJ},
      title = {INVOLVEMENT OF THE AMYGDALA IN LEARNING AND MEMORY - A CRITICAL-REVIEW, WITH EMPHASIS ON ANATOMICAL RELATIONS},
      journal = {BEHAVIORAL NEUROSCIENCE},
      publisher = {AMER PSYCHOLOGICAL ASSOC},
      year = {1985},
      volume = {99},
      number = {2},
      pages = {342-380}
    }
    
    Scammell, T., Estabrooke, I., McCarthy, M., Chemelli, R., Yanagisawa, M., Miller, M. & Saper, C. Hypothalamic arousal regions are activated during modafinil-induced wakefulness {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({22}), pp. {8620-8628} 
    article  
    Abstract: Modafinil is an increasingly popular wake-promoting drug used for the treatment of narcolepsy, but its precise mechanism of action is unknown. To determine potential pathways via which modafinil acts, we administered a range of doses of modafinil to rats, recorded sleep/wake activity, and studied the pattern of neuronal activation using Fos immunohistochemistry. To contrast modafinil-induced wakefulness with spontaneous wakefulness, we administered modafinil at midnight, during the normal waking period of rats. To determine the influence of circadian phase or ambient light, we also injected modafinil at noon on a normal light/dark cycle or in constant darkness. We found that 75 mg/kg modafinil increased Fos immunoreactivity in the tuberomammillary nucleus (TMN) and in orexin (hypocretin) neurons of the perifornical area, two cell groups implicated in the regulation of wakefulness. This low dose of modafinil also increased the number of Fos-immunoreactive (Fos-IR) neurons in the lateral subdivision of the central nucleus of the amygdala. Higher doses increased the number of Fos-IR neurons in the striatum and cingulate cortex. In contrast to previous studies, modafinil did not produce statistically significant increases in Fos expression in either the suprachiasmatic nucleus or the anterior hypothalamic area. These observations suggest that modafinil may promote waking via activation of TMN and orexin neurons, two regions implicated in the promotion of normal wakefulness. Selective pharmacological activation of these hypothalamic regions may represent a novel approach to inducing wakefulness.
    BibTeX:
    @article{Scammell2000,
      author = {Scammell, TE and Estabrooke, IV and McCarthy, MT and Chemelli, RM and Yanagisawa, M and Miller, MS and Saper, CB},
      title = {Hypothalamic arousal regions are activated during modafinil-induced wakefulness},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {22},
      pages = {8620-8628}
    }
    
    Schafe, G., Atkins, C., Swank, M., Bauer, E., Sweatt, J. & LeDoux, J. Activation of ERK/MAP kinase in the amygdala is required for memory consolidation of Pavlovian fear conditioning {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({21}), pp. {8177-8187} 
    article  
    Abstract: Although much has been learned about the neurobiological mechanisms underlying Pavlovian fear conditioning at the systems and cellular levels, relatively little is known about the molecular mechanisms underlying fear memory consolidation. The present experiments evaluated the role of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling cascade in the amygdala during Pavlovian fear conditioning. We first show that ERK/MAPK is transiently activated-phosphorylated in the amygdala, specifically the lateral nucleus (LA), at 60 min, but not 15, 30, or 180 min, after conditioning, and that this activation is attributable to paired presentations of tone and shock rather than to nonassociative auditory stimulation, foot shock sensitization, or unpaired tone-shock presentations. We next show that infusions of U0126, an inhibitor of ERK/MAPK activation, aimed at the LA, dose-dependently impair long-term memory of Pavlovian fear conditioning but leaves short-term memory intact. Finally, we show that bath application of U0126 impairs long-term potentiation in the LA in vitro. Collectively, these results demonstrate that ERK/MAPK activation is necessary for both memory consolidation of Pavlovian fear conditioning and synaptic plasticity in the amygdala.
    BibTeX:
    @article{Schafe2000,
      author = {Schafe, GE and Atkins, CM and Swank, MW and Bauer, EP and Sweatt, JD and LeDoux, JE},
      title = {Activation of ERK/MAP kinase in the amygdala is required for memory consolidation of Pavlovian fear conditioning},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {21},
      pages = {8177-8187}
    }
    
    SCHELL, M., MOLLIVER, M. & SNYDER, S. D-SERINE, AN ENDOGENOUS SYNAPTIC MODULATOR - LOCALIZATION TO ASTROCYTES AND GLUTAMATE-STIMULATED RELEASE {1995} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {92}({9}), pp. {3948-3952} 
    article  
    Abstract: Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we have localized endogenous D-serine in rat brain. Highest levels of D-serine immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus, anterior olfactory nucleus, olfactory tubercle, and amygdala, Localizations of D-serine immunoreactivity correlate closely with those of D-serine binding to the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor as visualized by autoradiography and are inversely correlated to the presence of D-amino acid oxidase, D-Serine is enriched in process-bearing glial cells in neuropil with the morphology of protoplasmic astrocytes. In glial cultures of rat cerebral cortex, D-serine is enriched in type 2 astrocytes. The release of D-serine from these cultures is stimulated by agonists of non-NMDA glutamate receptors, suggesting a mechanism by which astrocyte-derived D-serine could modulate neurotransmission. D-Serine appears to be the endogenous ligand for the glycine site of NMDA receptors.
    BibTeX:
    @article{SCHELL1995,
      author = {SCHELL, MJ and MOLLIVER, ME and SNYDER, SH},
      title = {D-SERINE, AN ENDOGENOUS SYNAPTIC MODULATOR - LOCALIZATION TO ASTROCYTES AND GLUTAMATE-STIMULATED RELEASE},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      publisher = {NATL ACAD SCIENCES},
      year = {1995},
      volume = {92},
      number = {9},
      pages = {3948-3952}
    }
    
    Schoenbaum, G., Chiba, A. & Gallagher, M. Neural encoding in orbitofrontal cortex and basolateral amygdala during olfactory discrimination learning {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({5}), pp. {1876-1884} 
    article  
    Abstract: Orbitofrontal cortex (OFC) is part of a network of structures involved in adaptive behavior and decision making. Interconnections between OFC and basolateral amygdala (ABL) may be critical for encoding the motivational significance of stimuli used to guide behavior. Indeed, much research indicates that neurons in OFC and ABL fire selectively to cues based on their associative significance. In the current study recordings were made in each region within a behavioral paradigm that allowed comparison of the development of associative encoding over the course of learning. In each recording session, vats were presented with novel odors that were informative about the outcome of making a response and had to learn to withhold a response after sampling an odor that: signaled a negative outcome. In some cases, reversal training was performed in the same session as the initial learning. Ninety-six of the 328 neurons recorded in OFC and 60 of the 229 neurons recorded in ABL exhibited selective activity during evaluation of the odor cues after learning had occurred. A substantial proportion of those neurons in ABL developed selective activity very early in training, and many reversed selectivity rapidly after reversal. In contrast, those neurons in OFC rarely exhibited selective activity during odor evaluation before the rats reached the criterion for learning,and far fewer reversed selectivity after reversal. The findings support a model in which ABL encodes the motivational significance of cues and OFC uses this information in the selection and execution of an appropriate behavioral strategy.
    BibTeX:
    @article{Schoenbaum1999,
      author = {Schoenbaum, G and Chiba, AA and Gallagher, M},
      title = {Neural encoding in orbitofrontal cortex and basolateral amygdala during olfactory discrimination learning},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {5},
      pages = {1876-1884}
    }
    
    Schoenbaum, G., Chiba, A. & Gallagher, M. Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning {1998} NATURE NEUROSCIENCE
    Vol. {1}({2}), pp. {155-159} 
    article  
    Abstract: Reciprocal connections between the orbitofrontal cortex and the basolateral nucleus of the amygdala may provide a critical circuit for the learning that underlies goal-directed behavior. We examined neural activity in rat orbitofrontal cortex and basolateral amygdala during instrumental learning in an olfactory discrimination task. Neurons in both regions fired selectively during the anticipation of rewarding or aversive outcomes. This selective activity emerged early in training, before the rats had learned reliably to avoid the aversive outcome. The results support the concept that the basolateral amygdala and orbitofrontal cortex cooperate to encode information that may be used to guide goal-directed behavior.
    BibTeX:
    @article{Schoenbaum1998,
      author = {Schoenbaum, G and Chiba, AA and Gallagher, M},
      title = {Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning},
      journal = {NATURE NEUROSCIENCE},
      publisher = {NATURE AMERICA INC},
      year = {1998},
      volume = {1},
      number = {2},
      pages = {155-159}
    }
    
    Schultz, R., Gauthier, I., Klin, A., Fulbright, R., Anderson, A., Volkmar, F., Skudlarski, P., Lacadic, C., Cohen, D. & Gore, J. Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome {2000} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {57}({4}), pp. {331-340} 
    article  
    Abstract: Background: Recognition of individual faces is an integral part of both interpersonal interactions and successful functioning within a social group. Therefore, it is of considerable interest that individuals with autism and related conditions have selective deficits in face recognition (sparing nonface object recognition). Method: We used functional magnetic resonance imaging (fMRI) to study face and subordinate-level object perception in 14 high-functioning individuals with autism or Asperger syndrome (the autism group), in comparison with 2 groups of matched normal controls (normal control group 1 [NC1] and normal control group 2 [NC2]) (n = 14 for each). Regions of interest (ROIs) were defined in NC1 and then applied in comparisons between NC2 and the autism group. Regions of interest were also defined in NC2 and then applied to comparisons between NC1 and the autism group as a replication study. Results: In the first set of comparisons, we found significant task X group interactions for the size of activation in the right fusiform gyrus (FC) and right inferior temporal gyri (ITG). Post hoc analyses showed that during face (but not object) discrimination, the autism group had significantly greater activation than controls in the right ITG and less activation of the right FG. The replication study showed again that the autism group used the ITG significantly more for processing faces than the control groups, but for these analyses, the effect was now on the left side. Greater ITG activation was the pattern found in both control groups during object processing. Conclusions: Individuals with autism spectrum disorders demonstrate a pattern of brain activity during face discrimination that is consistent with feature-based strategies that are more typical of nonface object perception.
    BibTeX:
    @article{Schultz2000,
      author = {Schultz, RT and Gauthier, I and Klin, A and Fulbright, RK and Anderson, AW and Volkmar, F and Skudlarski, P and Lacadic, C and Cohen, DJ and Gore, JC},
      title = {Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      publisher = {AMER MEDICAL ASSOC},
      year = {2000},
      volume = {57},
      number = {4},
      pages = {331-340},
      note = {1998 Biological Psychiatry Meeting, TORONTO, CANADA, MAY 28, 1998}
    }
    
    Schultz, W. Behavioral theories and the neurophysiology of reward {2006} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {57}, pp. {87-115} 
    article DOI  
    Abstract: The functions of rewards are based primarily on their effects on behavior and are less directly governed by the physics and chemistry of input events as in sensory systems. Therefore, the investigation of neural mechanisms underlying reward functions requires behavioral theories that can conceptualize the different effects of rewards on behavior. The scientific investigation of behavioral processes by animal learning theory and economic utility theory has produced a theoretical framework that can help to elucidate the neural correlates for reward functions in learning, goal-directed approach behavior, and decision making under uncertainty. Individual neurons can be studied in the reward systems of the brain, including dopamine neurons, orbitofrontal cortex, and striatum. The neural activity can be related to basic theoretical terms of reward and uncertainty, such as contiguity, contingency, prediction error, magnitude, probability, expected value, and variance.
    BibTeX:
    @article{Schultz2006,
      author = {Schultz, W},
      title = {Behavioral theories and the neurophysiology of reward},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      publisher = {ANNUAL REVIEWS},
      year = {2006},
      volume = {57},
      pages = {87-115},
      doi = {{10.1146/annurev.psych.56.091103.070229}}
    }
    
    Schultz, W. Getting formal with dopamine and reward {2002} NEURON
    Vol. {36}({2}), pp. {241-263} 
    article  
    Abstract: Recent neurophysiological studies reveal that neurons in certain brain structures carry specific signals about past and future rewards. Dopamine neurons display a short-latency, phasic reward signal indicating the difference between actual and predicted rewards. The signal is useful for enhancing neuronal processing and learning behavioral reactions. It is distinctly different from dopamine's tonic enabling of numerous behavioral processes. Neurons in the striatum, frontal cortex, and amygdala also process reward information but provide more differentiated information for identifying and anticipating rewards and organizing goal-directed behavior. The different reward signals have complementary functions, and the optimal use of rewards in voluntary behavior would benefit from interactions between the signals. Addictive psychostimulant drugs may exert their action by amplifying the dopamine reward signal.
    BibTeX:
    @article{Schultz2002,
      author = {Schultz, W},
      title = {Getting formal with dopamine and reward},
      journal = {NEURON},
      publisher = {CELL PRESS},
      year = {2002},
      volume = {36},
      number = {2},
      pages = {241-263}
    }
    
    Schultz, W. Predictive reward signal of dopamine neurons {1998} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {80}({1}), pp. {1-27} 
    article  
    Abstract: The effects of lesions, receptor blocking, electrical self-stimulation, and drugs of abuse suggest that midbrain dopamine systems are involved in processing reward information and learning approach behavior. Most dopamine neurons show phasic activations after primary liquid and food rewards and conditioned, reward-predicting visual and auditory stimuli. They show biphasic, activation-depression responses after stimuli that resemble reward-predicting stimuli or are novel or particularly salient. However, only few phasic activations follow aversive stimuli. Thus dopamine neurons label environmental stimuli with appetitive value, predict and detect rewards and signal alerting and motivating events. By failing to discriminate between different rewards, dopamine neurons appear to emit an alerting message about the surprising presence or absence of rewards. All responses to rewards and reward-predicting stimuli depend on event predictability. Dopamine neurons are activated by rewarding events that are better than predicted, remain uninfluenced by events that are as good as predicted, and are depressed by events that are worse than predicted. By signaling rewards according to a prediction error, dopamine responses have the formal characteristics of a teaching signal postulated by reinforcement learning theories. Dopamine responses transfer during learning from primary rewards to reward-predicting stimuli. This may contribute to neuronal mechanisms underlying the retrograde action of rewards, one of the main puzzles in reinforcement learning. The impulse response releases a short pulse of dopamine onto many dendrites, thus broadcasting a rather global reinforcement signal to postsynaptic neurons. This signal may improve approach behavior by providing advance reward information before the behavior occurs, and may contribute to learning by modifying synaptic transmission. The dopamine reward signal is supplemented by activity in neurons in striatum, frontal cortex, and amygdala, which process specific reward information but do not emit a global reward prediction error signal. A cooperation between the different reward signals may assure the use of specific rewards for selectively reinforcing behaviors. Among the other projection systems, noradrenaline neurons predominantly serve attentional mechanisms and nucleus basalis neurons code rewards heterogeneously. Cerebellar climbing fibers signal errors in motor performance or errors in the prediction of aversive events to cerebellar Purkinje cells. Most deficits following dopamine-depleting lesions are not easily explained by a defective reward signal but may reflect the absence of a general enabling function of tonic levels of extracellular dopamine. Thus dopamine systems may have two functions, the phasic transmission of reward information and the tonic enabling of postsynaptic neurons.
    BibTeX:
    @article{Schultz1998,
      author = {Schultz, W},
      title = {Predictive reward signal of dopamine neurons},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      publisher = {AMER PHYSIOLOGICAL SOC},
      year = {1998},
      volume = {80},
      number = {1},
      pages = {1-27}
    }
    
    Scott, S., Young, A., Calder, A., Hellawell, D., Aggleton, J. & Johnson, M. Impaired auditory recognition of fear and anger following bilateral amygdala lesions {1997} NATURE
    Vol. {385}({6613}), pp. {254-257} 
    article  
    Abstract: The amygdalar complex is a medial temporal lobe structure in the brain which is widely considered to be involved in the neural substrates of emotion, Selective bilateral damage to the human amygdala is rare, offering a unique insight into its functions. There is impairment of social perception after amygdala damage, with defective recognition of facial expressions of emotion(1-4). Among the basic emotions, the processing of fear and anger has been shown to be disrupted by amygdala damage(1,2,5). Although it remains puzzling why this not found in all cases(6), the importance of the amygdala in negative emotion, and especially fear, has been confirmed by conditioning(7), memory(8) and positron emission tomography (PET) experiments(9,10). Central to our understanding of these findings is the question of whether the amygdala is involved specifically in the perception of visual signals of emotion emanating from the face, or more widely in the perception of emotion in all sensory modalities(11). We report here a further investigation of one of these rare cases, a woman (D.R) who has impaired perception of the intonation patterns that are essential to the perception of vocal affect, despite normal hearing, As is the case for recognition of facial expressions, it is recognition of fear and anger that is most severely affected in the auditory domain, This shows that the amygdala's role in the recognition of certain emotions is not confined to vision, which is consistent with its being involved in the appraisal of danger and the emotion of fear(12,13).
    BibTeX:
    @article{Scott1997,
      author = {Scott, SK and Young, AW and Calder, AJ and Hellawell, DJ and Aggleton, JP and Johnson, M},
      title = {Impaired auditory recognition of fear and anger following bilateral amygdala lesions},
      journal = {NATURE},
      publisher = {MACMILLAN MAGAZINES LTD},
      year = {1997},
      volume = {385},
      number = {6613},
      pages = {254-257}
    }
    
    SEGUELA, P., WADICHE, J., DINELEYMILLER, K., DANI, J. & PATRICK, J. MOLECULAR-CLONING, FUNCTIONAL-PROPERTIES, AND DISTRIBUTION OF RAT BRAIN-ALPHA-7 - A NICOTINIC CATION CHANNEL HIGHLY PERMEABLE TO CALCIUM {1993} JOURNAL OF NEUROSCIENCE
    Vol. {13}({2}), pp. {596-604} 
    article  
    Abstract: A full-length clone coding for the rat alpha7 nicotinic receptor subunit was isolated from an adult brain cDNA library and expressed in Xenopus oocytes. A significant proportion of the current through alpha7-channels is carried by Ca2+. This Ca2+ influx then activates a Ca2+-dependent Cl- conductance, which is blocked by the chloride channel blockers niflumic and fluflenamic acid. Increasing the external NaCl concentration caused the reversal potentials for the alpha7-channels and the Ca2+-dependent Cl- channels to be shifted in opposite directions. Under these conditions, agonist application activates a biphasic current with an initial inward current through alpha7-channels followed by a niflumic acid- and fluflenamic acid-blockable outward current through Ca2+-dependent Cl- channels. A relative measure of the Ca2+ permeability was made by measuring the shift in the reversal potential caused by adding 10 mm Ca2+ to the external solution. Measurements made in the absence of Cl-, to avoid artifactual current through Ca2+-activated Cl- channels, indicate that alpha7-homooligomeric channels have a greater relative Ca2+ permeability than the other nicotinic ACh receptors. Furthermore, alpha7-channels have an even greater relative Ca2+ permeability than the NMDA subtype of glutamate receptors. High levels of alpha7-transcripts were localized by in situ hybridization in the olfactory areas, the hippocampus, the hypothalamus, the amygdala, and the cerebral cortex. These results imply that alpha7-containing receptors may play a role in activating calcium-dependent mechanisms in specific neuronal populations of the adult rat limbic system.
    BibTeX:
    @article{SEGUELA1993,
      author = {SEGUELA, P and WADICHE, J and DINELEYMILLER, K and DANI, JA and PATRICK, JW},
      title = {MOLECULAR-CLONING, FUNCTIONAL-PROPERTIES, AND DISTRIBUTION OF RAT BRAIN-ALPHA-7 - A NICOTINIC CATION CHANNEL HIGHLY PERMEABLE TO CALCIUM},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1993},
      volume = {13},
      number = {2},
      pages = {596-604}
    }
    
    SELDEN, N., EVERITT, B., JARRARD, L. & ROBBINS, T. COMPLEMENTARY ROLES FOR THE AMYGDALA AND HIPPOCAMPUS IN AVERSIVE-CONDITIONING TO EXPLICIT AND CONTEXTUAL CUES {1991} NEUROSCIENCE
    Vol. {42}({2}), pp. {335-350} 
    article  
    Abstract: Experiment 1 investigated the effects of catecholaminergic deafferentation or cell body lesions of the amygdala on fear conditioning to explicit and contextual cues. Bilateral infusions of quinolinic acid mainly damaged neurons within the basolateral region of the amygdala. 6-Hydroxydopamine infusions at the same coordinates resulted in an 86% depletion of noradrenaline and a 63% depletion of dopamine from the amygdala, but had no effect on the concentration of 5-hydroxytryptamine. After recovery from surgery, lesioned rats and controls were exposed to pairings of an auditory (clicker) conditioned stimulus and (foot shock) unconditioned stimulus in a distinctive environment. During testing, rats with both 6-hydroxydopamine and cell body lesions showed severely impaired conditioning to explicit cues, compared with controls, indicated by their reduced suppression of drinking when the conditioned stimulus was introduced into a separate, lick-operant chamber. Neither lesion affected fear conditioning to contextual cues, measured as preference for a ``safe'' environment over the one in which they were shocked. In Experiment 2, rats received bilateral, ibotenic acid-induced lesions of the hippocampal formation. Lesioned rats and controls were again tested for aversive conditioning to explicit and contextual cues. Rats with cell body lesions of the hippocampus showed normal suppression of drinking in the presence of the conditioned stimulus, but were severely impaired in choosing the safe environment based on contextual cues alone. These results suggest a double dissociation of the effects of amygdala and hippocampal damage on fear conditioning to explicit and contextual cues.
    BibTeX:
    @article{SELDEN1991,
      author = {SELDEN, NRW and EVERITT, BJ and JARRARD, LE and ROBBINS, TW},
      title = {COMPLEMENTARY ROLES FOR THE AMYGDALA AND HIPPOCAMPUS IN AVERSIVE-CONDITIONING TO EXPLICIT AND CONTEXTUAL CUES},
      journal = {NEUROSCIENCE},
      publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
      year = {1991},
      volume = {42},
      number = {2},
      pages = {335-350}
    }
    
    SEMBA, K. & FIBIGER, H. AFFERENT CONNECTIONS OF THE LATERODORSAL AND THE PEDUNCULOPONTINE TEGMENTAL NUCLEI IN THE RAT - A RETROGRADE AND ANTEROGRADE TRANSPORT AND IMMUNOHISTOCHEMICAL STUDY {1992} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {323}({3}), pp. {387-410} 
    article  
    Abstract: Increasingly strong evidence suggests that cholinergic neurons in the mesopontine tegmentum play important roles in the control of wakefulness and sleep. To understand better how the activity of these neurons is regulated, the potential afferent connections of the laterodorsal (LDT) and pedunculopontine tegmental nuclei (PPT) were investigated in the rat. This was accomplished by using retrograde and anterograde axonal transport methods and NADPH-diaphorase histochemistry. Immunohistochemistry was also used to identify the transmitter content of some of the retrogradely identified afferents. Following injections of the retrograde tracer wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) into either the LDT or the PPT, labelled neurons were seen in a number of limbic forebrain structures. The medial prefrontal cortex and lateral habenula contained more retrogradely labelled neurons from the LDT, whereas in the bed nucleus of the stria terminalis and central nucleus of the amygdala, more cells were labelled from the PPT. Moderate numbers of neurons were seen in the magnocellular regions of the basal forebrain, and many labelled neurons were observed in the lateral hypothalamus, the zona incerta, and the midbrain central gray from both the LDT and the PPT. Accessory oculomotor nuclei in the midbrain as well as eye movement-related structures in the lower brainstem contained some neurons labelled from the LDT, and fewer neurons from the PPT. A few labelled neurons were seen in somatosensory and other sensory relay nuclei in the brainstem and the spinal cord. Retrograde labelling was seen in a number of extrapyramidal structures, including the globus pallidus, entopenduncular and subthalamic nuclei, and substantia nigra following PPT injections; with LDT injections, labelling was similar in density in the substantia nigra but virtually absent in the entopeduncular and subthalamic nuclei. Data with the fluorescent retrograde tracer fluorogold combined with immunofluorescence indicated that many neurons in the zona incerta-lateral hypothalamic region that were retrogradely labelled from the LDT contained a-melanocyte-stimulating hormone. Numerous neurons were labelled throughout the reticular formation of the brainstem following either LDT or PPT injections. Many neurons retrogradely labelled in the LDT and PPT, the dorsal and median raphe nuclei, and the locus ceruleus contained choline acetyltransferase, serotonin, and tyrosine hydroxylase, respectively. The anterograde tracers WGA-HRP and phaseolus vulgaris leucoagglutinin were used to confirm some of the projections indicated by the retrograde labelling data; anterograde labelling was seen in the LDT and PPT following injections of one of these tracers into the medial prefrontal cortex, lateral hypothalamus, and the contralateral LDT. NADPH-diaphorase histochemistry combined with immunohistochemistry indicated that serotonin- and tyrosine hydroxylase-immunoreactive fibers bearing occasional swellings were closely associated with NADPH-diaphorase-positive, cholinergic neurons in the LDT and PPT. These data suggest that potential afferents to the LDT and the PPT arise in many common, but also some separate structures in the forebrain, brainstem, and spinal cord. Both the LDT and the PPT appear to receive heavy inputs from three structures: brainstem reticular formation, midbrain central gray, and lateral hypothalamus-zona incerta region. Other, less prominent afferents originate in a number of limbic, oculomotor, extrapyramidal, and sensory structures, with some degrees of preference for the LDT or PPT. Some of the reticular connections with the LDT and PPT are serotoninergic or noradrenergic. The reticuloreticular network also includes commissural and rostrocaudal cholinergic interconnections between the LDT and PPT. The apparent similarities in both the afferent and efferent connections of the LDT and the PPT are consistent with the working hypothesis that cholinergic neurons in the mesopontine tegmentum represent a single functional unit. The potential afferent connections identified in the present study also suggest that the PPT and LDT are involved in the regulation of behavioral state.
    BibTeX:
    @article{SEMBA1992,
      author = {SEMBA, K and FIBIGER, HC},
      title = {AFFERENT CONNECTIONS OF THE LATERODORSAL AND THE PEDUNCULOPONTINE TEGMENTAL NUCLEI IN THE RAT - A RETROGRADE AND ANTEROGRADE TRANSPORT AND IMMUNOHISTOCHEMICAL STUDY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      publisher = {WILEY-LISS},
      year = {1992},
      volume = {323},
      number = {3},
      pages = {387-410}
    }
    
    Sheline, Y., Barch, D., Donnelly, J., Ollinger, J., Snyder, A. & Mintun, M. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: An fMRI study {2001} BIOLOGICAL PSYCHIATRY
    Vol. {50}({9}), pp. {651-658} 
    article  
    Abstract: Background: The amygdala has a central role in processing emotions, particularly fear. During functional magnetic resonance imaging (fMRI) amygdala activation has been demonstrated outside of conscious awareness using masked emotional faces. Methods: We applied the masked faces paradigm to patients with major depression (n = 11) and matched control subjects (n = 11) during fMRI to compare amygdala activation in response to masked emotional faces before and after antidepressant treatment. Data were analyzed using left and right amygdala a priori regions of interest, in an analysis of variance block analysis and random effects model. Results: Depressed patients had exaggerated left amygdala activation to all faces, greater for fearful faces. Right amygdala did not differ from control subjects. Following treatment, patients had bilateral reduced amygdala activation to masked fearful faces and bilateral reduced amygdala activation to all faces. Control subjects had no differences between the two scanning sessions. Conclusions: Depressed patients have left amygdala hyperarousol, even when processing stimuli outside conscious awareness. Increased amygdala activation normalizes with antidepressant treatment. (C) 2001 Society of Biological Psychiatry.
    BibTeX:
    @article{Sheline2001,
      author = {Sheline, YI and Barch, DM and Donnelly, JM and Ollinger, JM and Snyder, AZ and Mintun, MA},
      title = {Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: An fMRI study},
      journal = {BIOLOGICAL PSYCHIATRY},
      publisher = {ELSEVIER SCIENCE INC},
      year = {2001},
      volume = {50},
      number = {9},
      pages = {651-658}
    }
    
    Sheline, Y., Gado, M. & Price, J. Amygdala core nuclei volumes are decreased in recurrent major depression {1998} NEUROREPORT
    Vol. {9}({9}), pp. {2023-2028} 
    article  
    Abstract: THE amygdala is a key structure in the brain's integration of emotional meaning with perception and experience.(1) Patients with depression have impaired functioning in emotional tasks involving the amygdala,(2) and have abnormal resting amygdala blood flow.(3) To better understand the anatomical basis for these functional changes we measured the volumes of the total amygdala and of the core amygdala nuclei in 20 patients with a history of depression and 20 pair-wise matched controls. Depressed subjects had bilaterally reduced amygdala core nuclei volumes and no significant differences in total amygdala volumes or in whole brain volumes. Since patients with a depression history have bilateral hippocampal volume reduction(4) the volume loss in this closely related structure suggests a shared effect on bo th structures, potentially glucocorticoid-induced neurotoxicity(5) mediated by the extensive reciprocal glutamatergic connections. (C) 1998 Rapid Science Ltd.
    BibTeX:
    @article{Sheline1998,
      author = {Sheline, YI and Gado, MH and Price, JL},
      title = {Amygdala core nuclei volumes are decreased in recurrent major depression},
      journal = {NEUROREPORT},
      publisher = {LIPPINCOTT WILLIAMS & WILKINS},
      year = {1998},
      volume = {9},
      number = {9},
      pages = {2023-2028}
    }
    
    Sheline, Y., Sanghavi, M., Mintun, M. & Gado, M. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({12}), pp. {5034-5043} 
    article  
    Abstract: This study takes advantage of continuing advances in the precision of magnetic resonance imaging (MRI) to quantify hippocampal volumes in a series of human subjects with a history of depression compared with controls. We sought to test the hypothesis that both age and duration of past depression would be inversely and independently correlated with hippocampal volume. A sample of 24 women ranging in age from 23 to 86 years with a history of recurrent major depression, but no medical comorbidity, and 24 case-matched controls underwent MRI scanning. Subjects with a history of depression (post-depressed) had smaller hippocampal volumes bilaterally than controls. Post-depressives also had smaller amygdala core nuclei volumes, and these volumes correlated with hippocampal volumes. In addition, post-depressives scored lower in verbal memory, a neuropsychological measure of hippocampal function, suggesting that the volume loss was related to an aspect of cognitive functioning. In contrast, there was no difference in overall brain size or general intellectual performance. Contrary to our initial hypothesis, there was no significant correlation between hippocampal volume and age in either post-depressive or control subjects, whereas there was a significant correlation with total lifetime duration of depression. This suggests that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss.
    BibTeX:
    @article{Sheline1999,
      author = {Sheline, YI and Sanghavi, M and Mintun, MA and Gado, MH},
      title = {Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression},
      journal = {JOURNAL OF NEUROSCIENCE},
      publisher = {SOC NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {12},
      pages = {5034-5043}
    }
    
    Shenton, M., Dickey, C., Frumin, M. & McCarley, R. A review of MRI findings in schizophrenia {2001} SCHIZOPHRENIA RESEARCH
    Vol. {49}({1-2}), pp. {1-52} 
    article  
    Abstract: After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin, E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described `dementia praecox' and the schizophrenias', were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82-120) was the first to investigate the neuropathology of schizophrenia, though he went on to study mon tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon. M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137-147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus. and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly. there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi-92% of studies reviewed, basal ganglia-68% of studies reviewed, corpus callosum-63% of studies reviewed, and thalamus-42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed).
    BibTeX:
    @article{Shenton2001,
      author = {Shenton, ME and Dickey, CC and Frumin, M and McCarley, RW},
      title = {A review of MRI findings in schizophrenia},
      journal = {SCHIZOPHRENIA RESEARCH},
      publisher = {ELSEVIER SCIENCE BV},
      year = {2001},
      volume = {49},
      number = {1-2},
      pages = {1-52}
    }
    
    SHENTON, M., KIKINIS, R., JOLESZ, F., POLLAK, S., LEMAY, M., WIBLE, C., HOKAMA, H., MARTIN, J., METCALF, D., COLEMAN, M. & MCCARLEY, R. ABNORMALITIES OF THE LEFT TEMPORAL-LOBE AND THOUGHT-DISORDER IN SCHIZOPHRENIA - A QUANTITATIVE MAGNETIC-RESONANCE-IMAGING STUDY {1992} NEW ENGLAND JOURNAL OF MEDICINE
    Vol. {327}({9}), pp. {604-612} 
    article  
    Abstract: Background. Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia. Methods. We used new MRI neuroimaging techniques to derive (without knowledge of the diagnosis) volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls. Results. As compared with the controls, the patients had significant reductions in the volume of gray matter in the left anterior hippocampus-amygdala (by 19 percent [95 percent confidence interval, 3 to 36 percent]), the left parahippocampal gyrus (by 13 percent [95 percent confidence interval, 3 to 23 percent], vs. 8 percent on the right), and the left superior temporal gyrus (by 15 percent [95 percent confidence interval, 5 to 25 percent]). The volume of the left posterior superior temporal gyrus correlated with the score on the thought-disorder index in the 13 patients evaluated (r = -0.81, P = 0.001). None of these regional volume decreases were accompanied by a decrease in the volume of the overall brain or temporal lobe. The volume of gray matter in a control region (the superior frontal gyrus) was essentially the same in the patients and controls. Conclusions. Schizophrenia involves localized reductions in the gray matter of the left temporal lobe. The degree of thought disorder is related to the size of the reduction in volume of the left posterior superior temporal gyrus.
    BibTeX:
    @article{SHENTON1992,
      author = {SHENTON, ME and KIKINIS, R and JOLESZ, FA and POLLAK, SD and LEMAY, M and WIBLE, CG and HOKAMA, H and MARTIN, J and METCALF, D and COLEMAN, M and MCCARLEY, RW},
      title = {ABNORMALITIES OF THE LEFT TEMPORAL-LOBE AND THOUGHT-DISORDER IN SCHIZOPHRENIA - A QUANTITATIVE MAGNETIC-RESONANCE-IMAGING STUDY},
      journal = {NEW ENGLAND JOURNAL OF MEDICINE},
      publisher = {MASS MEDICAL SOC},
      year = {1992},
      volume = {327},
      number = {9},
      pages = {604-612}
    }
    
    Shin, L., Kosslyn, S., McNally, R., Alpert, N., Thompson, W., Rauch, S., Macklin, M. & Pitman, R. Visual imagery and perception in posttraumatic stress disorder - A positron emission tomographic investigation {1997} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {54}({3}), pp. {233-241} 
    article  
    Abstract: Background: Relative regional cerebral blood flow (rCBF) changes were measured in Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) during exposure to combat-related stimuli. Methods: Positron emission tomography was used to measure rCBF in 7 combat veterans with PTSD (PTSD group) and 7 healthy combat veterans (control group) who viewed and generated visual mental images of neutral, negative, and combat-related pictures. Results: Unlike control subjects, subjects with PTSD had increased rCBF in ventral anterior cingulate gyrus and right amygdala when generating mental images of combat-related pictures; when viewing combat pictures, subjects with PTSD showed decreased rCBF in Broca's area. Conclusions: Results suggest that ventral anterior cingulate gyrus and right amygdala play a role in the response of combat veterans with PTSD to mental images of combat-related scenes. Reexperiencing phenomena of PTSD, which often involve emotional visual mental imagery, may be likewise associated with increased rCBF in these regions.
    BibTeX:
    @article{Shin1997,
      author = {Shin, LM and Kosslyn, SM and McNally, RJ and Alpert, NM and Thompson, WL and Rauch, SL and Macklin, ML and Pitman, RK},
      title = {Visual imagery and perception in posttraumatic stress disorder - A positron emission tomographic investigation},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      publisher = {AMER MEDICAL ASSOC},
      year = {1997},
      volume = {54},
      number = {3},
      pages = {233-241},
      note = {10th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies, CHICAGO, IL, NOV 05-09, 1994}
    }
    
    Shin, L., McNally, R., Kosslyn, S., Thompson, W., Rauch, S., Alpert, N., Metzger, L., Lasko, N., Orr, S. & Pitman, R. Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation {1999} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {156}({4}), pp. {575-584} 
    article  
    Abstract: Objective: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). Method: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. Results: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. Conclusions: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.
    BibTeX:
    @article{Shin1999,
      author = {Shin, LM and McNally, RJ and Kosslyn, SM and Thompson, WL and Rauch, SL and Alpert, NM and Metzger, LJ and Lasko, NB and Orr, SP and Pitman, RK},
      title = {Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      publisher = {AMER PSYCHIATRIC PRESS, INC},
      year = {1999},
      volume = {156},
      number = {4},
      pages = {575-584},
      note = {Conference on Psychobiology of Posttraumatic Stress Diso