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Synaptic Plasticity and Extinction of Fear


Kerry J. Ressler, MD, PhD is an assistant professor in the Department of Psychiatry and Behavioral Sciences at Emory University. As a psychiatrist trained in molecular biology and neurobiology, his driving interest has been the understanding of neural systems that undedie behavior and emotion. Following residency, he started a laboratory at Emory's Yerkes Research Center in the Center for Behavioral Neuroscience to focus on molecular mechanisms of amygdala functioning. Dr. Ressler is now in an optimal position to complete his training in behavioral neuroscience with Dr. Michael Davis, a leader in the field, as a mentor. The Mentored Research Scientist Development Award is perfectly suited to assist in his career development, so that he may become a productive researcher with full training in molecular and behavioral neurobiology that is also informed by his psychiatry training and experience. Dr. Ressler spends approximately 15% of his time directing a clinic specializing in the treatment of Post-traumatic Stress Disorder (PTSD), a disorder of fear dyregulation. Treatment of PTSD, as well as phobia, panic disorder, and other anxiety disorders depends upon the teaming process of extinction -- the primary mechanism by which learned fear is reduced. It is now known that extinction is an active process of inhibitory learning that involves synaptic plasticity and that may occur within the amygdala and the infralimbic prefrontal cortex, an area that modulates amygdata activity. The specific aims of this proposal will investigate the role of calcium dependent synaptic plasticity in mediating extinction learning in the amygdala and prefrontal cortex. It is thought that calcium entry through the NMDA receptor (NMDAR) and the L-type voltage gated calcium channel (VGCC) may have different functions during the consolidation of extinction. These experiments will first identify synaptic plasticity genes involved in the consolidation of extinction. This will be followed by behavioral and gene expression analyses of extinction following facilitation or inhibition of extinction with NMDAR and VGCC agonists and antagonists. Finally, gene expression and cell-type specificity will be examined by using viral mediated gene transfer of dominant negative or facilitatory mutant subunits of the NMDAR and VGCC channels. Understanding the molecular mechanisms of extinction will be important both for advancing the fundamental understanding of learning and memory as well as for providing novel approaches to treating human disorders of fear dysregulation. Furthermore, this project will provide opportunity to significantly develop Dr. Ressler's expertise and technical skills in behavioral neuroscience, including design, training, and testing of rodents, viral vector techniques, and analysis of gene expression using gene array techniques. Emory University and the Center for Behavioral Neuroscience provide an excellent environment for career development and training in the field of behavioral neuroscience.

Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.