P 5/7: Deconstructing the role of extended amygdala circuits in stress regulated alcohol drinking

Thomas Kash

PROJECT SUMMARY
A growing literature indicates that chronic alcohol exposure leads to recruitment of central stress systems, such as corticotrophin releasing factor (CRF) and Dynorphin (DYN), in key brain circuits including the bed nucleus of the stria terminalis (BNST) and Central nucleus of the amygdala (CeA), leading to altered functional connectivity and pathological behavior. However, there remains a gap in our knowledge of the broader circuit mechanisms that contribute to this dysregulated behavior. Our goal is to identify alcohol induced adaptations in stress circuitry to provide a circuit based template for treatment of alcohol use disorders and co-morbid conditions. In the previous funding period, we found that activation of CRF neurons in the BNST are required for excessive alcohol consumption. Here, we propose to determine the impact of intermittent alcohol exposure and stress on plasticity in subpopulations of neurons in both the BNST and the CeA. The central hypothesis to be tested is that repeated alcohol exposure leads to increased stress induced recruitment of extended amygdala CRF and DYN, driving pathological behavior.