6/8: INIA Stress and Chronic Alcohol Interactions: Deconstructing the role of extended amygdala circuits in stress regulated alcohol drinking

越来越多的文献表明，慢性酒精暴露导致招募的中央压力 系统，如促肾上腺皮质激素释放因子（CRF）和强啡肽（DYN），在关键脑 包括终纹床核（BNST）和中央核的回路 杏仁核（CeA），导致改变功能连接和病理行为。然而，在这方面， 在我们对更广泛的电路机制的知识方面仍然存在差距， 行为失调我们的目标是确定酒精诱导的适应压力电路， 为酒精使用障碍和共病的治疗提供基于回路的模板 条件在上一个资助期，我们发现BNST中CRF神经元的激活 是过量饮酒所必需的在这里，我们建议确定 间歇性酒精暴露和压力对神经元亚群的可塑性， BNST和CeA。有待检验的中心假设是，反复饮酒会导致 增加应激诱导的扩展杏仁核CRF和DYN的募集，驾驶 病态行为

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.