Director: Chitra Mandyam, Ph.D.
The Cellular Physiology Research Component will focus on the hypothesis that aberrant neurogenesis during withdrawal contributes to recruitment of BLA-hippocampal emotional memory circuits and that inhibiting this process will enhance recovery by reducing withdrawal-associated behaviors. To test this hypothesis, Specific Aim 1 is designed to determine how neural stem cells in the hippocampal dentate gyrus (DG) are altered during early withdrawal from the CIE dependence model. Specific Aim 2 is designed to evaluate the synaptic activity and morphology of granule cell neurons (GCNs) born during withdrawal and correlate the changes with withdrawal-associated behavior. Specific Aim 3 is designed to determine whether inhibiting excitatory CRF1-glutamatergic signaling in the BLA inhibits withdrawal-associated behavior and aberrant DG neurogenesis. Retroviral vectors will be produced by the Viral Vector Core. Electrophysiological studies will be performed in collaboration with Dr. Roberto, and anxiety-like behavior and CRF1 knockdown studies will be performed in collaboration with Drs. Zorrilla and Contet.