Alcohol action on extended amygdala glutamate synapses

摘要 酒精使用障碍(AUD)是我们社会的一个巨大的健康和经济负担。成长中的文学作品 表明延长的杏仁核在压力-奖赏相互作用中起关键作用，这可能是关键的中介。 慢性酒精暴露的行为反应。我们证明了慢性间歇性酒精暴露 上调CRF受体依赖的谷氨酸释放增加，以及突触后NMDA 延伸的杏仁核谷氨酸突触上的受体功能。我们建议在这里测试“两次点击”模式， 因此，慢性酒精暴露和戒断所产生的情感障碍取决于 延伸的杏仁核谷氨酸突触的突触前和突触后协调调节。为了加强这一点 根据学员的研究经验和发展，我们提出了一系列实验来绘制机制 通过这种方式，BNST(来自脑岛)的谷氨酸输入可以通过改变 对这些细胞的兴奋性和抑制性驱动。她将在强制禁欲模型中探索这些机制 慢性酒精暴露，获得体外成像和电生理训练，以及治疗经验 啮齿动物酒精暴露模型。指导还将侧重于通过手稿进行沟通的技能 为科学会议准备和准备海报。

Abstract Alcohol Use Disorder (AUD) is a tremendous health and financial burden on our society. A growing literature indicates that the extended amygdala plays a key role in stress-reward interactions that may mediate key behavioral responses to chronic alcohol exposure. We demonstrated that chronic intermittent alcohol exposure up regulates CRF receptor dependent augmentation of glutamate release, as well as postsynaptic NMDA receptor function at extended amygdala glutamate synapses. We propose here to test a "two-hit" model, whereby affective disruptions produced by chronic alcohol exposure and withdrawal depend upon the coordinated pre- and postsynaptic regulation of extended amygdala glutamate synapses. To enhance this trainee’s research experience and development, we propose a series of experiments to map out mechanisms by which glutamateric inputs to the BNST (from the insula) may be organized and recruited via changes in excitatory and inhibitory drive on these cells. She will explore these mechanisms in a forced abstinence model of chronic alcohol exposure, gaining ex vivo imaging and electrophysiological training, and experience with rodent alcohol exposure models. Mentorship will also focus on communication skills through manuscript preparation and preparation of posters for scientific conferences.