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

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

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dc.contributor.advisor Nester, Eric J. en
dc.creator Krishnan, Vaishnav en
dc.date.accessioned 2010-07-12T18:53:17Z en
dc.date.available 2010-07-12T18:53:17Z en
dc.date.issued 2010-05-14 en
dc.identifier.other 795706969 en
dc.identifier.uri http://hdl.handle.net/2152.5/708 en
dc.description.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. en
dc.language.iso en en
dc.subject.mesh Psychiatry en
dc.subject.mesh Disease Models, Animal en
dc.subject.mesh Research en
dc.title Vulnerability and Resilience to Social Defeat: The Role of Neuroplasticity Within the Mesolimbic Dopamine Circuit en
thesis.degree.grantor Graduate School of Biomedical Sciences en
thesis.degree.name Doctor of Philosophy en
thesis.degree.level Ph.D. en
thesis.degree.discipline Neuroscience en
thesis.date.available 2010-05-14 en

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