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

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dc.contributor.advisorNestler, Eric J.en
dc.creatorKrishnan, Vaishnaven
dc.date.accessioned2010-07-12T18:53:17Z
dc.date.available2010-07-12T18:53:17Z
dc.date.issued2010-05-14
dc.description.abstractThe 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.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc795706969
dc.identifier.urihttps://hdl.handle.net/2152.5/708
dc.language.isoenen
dc.subjectPsychiatryen
dc.subjectDisease Models, Animalen
dc.subjectResearchen
dc.titleVulnerability and Resilience to Social Defeat: The Role of Neuroplasticity Within the Mesolimbic Dopamine Circuiten
dc.typeThesisen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2010-05-14
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineNeuroscienceen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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