Vulnerability and Resilience to Social Defeat: The Role of Neuroplasticity Within the Mesolimbic Dopamine Circuit

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Title: Vulnerability and Resilience to Social Defeat: The Role of Neuroplasticity Within the Mesolimbic Dopamine Circuit
Author: Krishnan, Vaishnav
Abstract: The pathophysiology of major depression and post -traumatic stress disorder are poorly understood . In particular , while stressful life events are an important cause of psychopathology , most individuals exposed to adversity maintain normal psychological functioning . The molecular mechanisms underlying this “resilience” are poorly understood . Here , we demonstrate that an inbred population of mice subjected to social defeat can be separated into susceptible and unsusceptible subpopulations which differ along several behavioral and physiological domains . Through a series of molecular and electrophysiological techniques , we identify signature adaptations within the mesolimbic dopamine circuit that are uniquely associated with vulnerability and , by a combination of viral -mediated gene transfer and genetic mouse models , we demonstrate how these adaptations are causally linked to a vulnerable phenotype . We also show that molecular recapitulations of adaptations associated with the unsusceptible phenotype are sufficient to promote resilient behavior . Our results validate a multidisciplinary approach to examine the neurobiological mechanisms of variations in stress resistance , and illustrate the importance of plasticity within the brain’s reward circuits in actively maintaining an emotional homeostasis .
URI: http : / /hdl .handle .net /2152 .5 /708
Date: 2010-05-14

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Vulnerability and Resilience to Social Defeat: The Role of Neuroplasticity Within the Mesolimbic Dopamine Circuit. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /708 .

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