CRF NEURAL CIRCUITS OF BINGE DRINKING

项目摘要/摘要 酗酒是一个严重的公共健康问题，是可预防的第三大原因。 美国的死亡(Hingson等人，2005；2007)。定义调节过度狂欢的神经回路 酒精摄入对于开发有效的治疗方法来治疗这种疾病是必不可少的。促肾上腺皮质激素释放 促肾上腺皮质激素释放因子(CRF)是一种重要的神经肽，与酗酒作为外周和部位- 特定剂量的CRF拮抗剂可以减少过量的乙醇摄入(Sparta等人，2008；2009； 2013)。虽然CRF在整个大脑中都被发现，但延伸的杏仁核由中央核团组成。 杏仁核(CEA)和终纹床核(BNST)CRF向腹侧被盖投射 面积(VTA)仍然是CRF调节酗酒的一个特别有趣的候选靶点，因为 这些结构提供了从压力到奖励大脑区域的直接联系，我假设狂欢 酒精暴露导致杏仁核CRF神经元向VTA GABA神经元的驱动增加。 具体地说，我假设CRF CEA到VTA的投射是在反复酗酒时招募的 而CRF BNST到VTA的通路参与了酗酒的开始。为了测试 这些假说，我将利用光遗传学、体内电生理学、体外膜片钳和行为学。 综上所述，该提案将全面描述CEA-和BNST-VTA CRF 过量饮酒后的神经回路，并可能确定治疗糖尿病的可能药物靶点 酗酒。

Project Summary/Abstract Binge alcohol consumption is a severe public health problem and is the third leading cause of preventable death in the USA (Hingson et al., 2005; 2007). Defining the neural circuitry that modulates excessive binge alcohol intake is essential for developing effective therapeutics to treat this disease. Corticotropin releasing factor (CRF) is an important neuropeptide, in regards to binge alcohol consumption as peripheral and site- specific administrations of CRF antagonists can reduce excessive ethanol intake (Sparta et al., 2008; 2009; 2013). While CRF is found throughout the brain, the extended amygdala consisting of the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST) CRF projections the to ventral tegmental area (VTA) remain a particularly interesting candidate targets for CRF’s modulation of binge drinking, since these structures provide direct connections from stress to reward brain regions I hypothesize that binge alcohol exposure leads to an increase of extended amygdalar CRF neuronal drive onto VTA GABA neurons. Specifically, I hypothesize that the CRF CeA to VTA projection is recruited during repeated binge drinking sessions, whereas the CRF BNST to VTA pathway is involved with the initiation of binge drinking. To test these hypotheses, I will utilize optogenetics, in vivo electrophysiology, ex vivo patch clamp, and behavior. Taken together, this proposal will provide a thorough characterization of both the CeA-and BNST-VTA CRF neural circuits after binge alcohol intake and may identify possible pharmacological targets for the treatment of alcoholism.