Alcohol action on extended amygdala glutamate synapses

摘要 酒精使用障碍 (AUD) 给我们的社会带来了巨大的健康和经济负担。不断增长的文学 表明扩展的杏仁核在压力-奖励相互作用中发挥着关键作用，可能调解关键 对长期酒精暴露的行为反应。我们证明，慢性间歇性酒精暴露 上调 CRF 受体依赖性谷氨酸释放增强以及突触后 NMDA 扩展杏仁核谷氨酸突触的受体功能。我们在这里建议测试“两次打击”模型， 长期接触酒精和戒断造成的情感破坏取决于 扩展杏仁核谷氨酸突触的突触前和突触后协调调节。为了增强这一点 根据受训者的研究经验和发展，我们提出了一系列实验来制定机制 通过这种方式，可以通过改变来组织和招募 BNST（来自岛）的谷氨酸输入 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，获得离体成像和电生理训练，以及经验 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技巧 科学会议海报的准备和制作。

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.