The Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala During the First Extinction Episode Has Persistent Effects on Extinction Expression |
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| Affiliation: | 1. Center for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montreal, Québec, Canada;2. Sussex Neuroscience, School of Psychology, University of Sussex, Falmer, United Kingdom;3. Behavioral Neuroscience Branch Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland;4. Department of Psychology, Brooklyn College of the City University of New York, Brooklyn, New York;1. Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, Ohio;2. Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio;1. School of Psychology, UNSW Sydney, 2052, Australia;2. The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 3052, Australia;3. Department of Anatomy and Neurosciences, VU University Medical Center Amsterdam, 1081 BT, Netherlands;4. Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, UNSW Sydney, 2052, Australia;1. Neural Systems Laboratory, Department of Health Sciences, Boston University, Boston, Massachusetts;2. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts;3. Institute of Computational Neuroscience, University Medical Center Eppendorf, Hamburg University, Hamburg, Germany;1. Department of Psychology, University of California, Davis, Davis, California;2. Bioinformatics Core Facility, UC Davis Genome Center, University of California, Davis, Davis, California;3. Department of Public Health Sciences, University of California, Davis, California;4. Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York;5. Princeton Neuroscience Institute, Princeton, New Jersey;6. Department of Psychology, Temple University, Philadelphia, Pennsylvania;7. Gene Delivery Technology Core, Massachusetts General Hospital, Boston, Massachusetts;8. Department of Psychiatry and Neuroscience, Laval University, Québec, Quebec, Canada;1. Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri;2. Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri;3. Department of Neuroscience, Washington University in St. Louis, St. Louis, Missouri;4. Department of Economics, Georgetown University, Washington, DC;1. Fralin Biomedical Research Institute at Virginia Tech Carilion Center for Neurobiology Research, Roanoke, Virginia;2. Carilion Clinic Department of Psychiatry and Behavioral Medicine, Roanoke, Virginia |
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| Abstract: | BackgroundAdaptive behavior depends on the delicate and dynamic balance between acquisition and extinction memories. Disruption of this balance, particularly when the extinction of memory loses control over behavior, is the root of treatment failure of maladaptive behaviors such as substance abuse or anxiety disorders. Understanding this balance requires a better understanding of the underlying neurobiology and its contribution to behavioral regulation.MethodsWe microinjected Daun02 in Fos-lacZ transgenic rats following a single extinction training episode to delete extinction-recruited neuronal ensembles in the basolateral amygdala (BLA) and central nucleus of the amygdala (CN) and examined their contribution to behavior in an appetitive Pavlovian task. In addition, we used immunohistochemistry and neuronal staining methods to identify the molecular markers of activated neurons in the BLA and CN during extinction learning or retrieval.ResultsCN neurons were preferentially engaged following extinction, and deletion of these extinction-activated ensembles in the CN but not the BLA impaired the retrieval of extinction despite additional extinction training and promoted greater levels of behavioral restoration in spontaneous recovery and reinstatement. Disrupting extinction processing in the CN in turn increased activity in the BLA. Our results also show a specific role for CN PKCδ+ neurons in behavioral inhibition but not during initial extinction learning.ConclusionsWe showed that the initial extinction-recruited CN ensemble is critical to the acquisition-extinction balance and that greater behavioral restoration does not mean weaker extinction contribution. These findings provide a novel avenue for thinking about the neural mechanisms of extinction and for developing treatments for cue-triggered appetitive behaviors. |
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| Keywords: | Amygdala Appetitive Conflict Engram Memory Reward |
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