Alcohol action on extended amygdala glutamate synapses

酒精对延长杏仁核谷氨酸突触的作用

• 批准号: 10515868
• 负责人: DANNY G WINDER
• 金额: $ 3.32万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10515868
• 关键词: Abstinence; Affective; Alcohol withdrawal syndrome; Alcohols; Amygdaloid structure; Cells; Chronic; Communication; Corticotropin-Releasing Hormone Receptors; Development; Electrophysiology (science); Financial Hardship; Glutamates; Health; Insula of Reil; Literature; Manuscripts; Maps; Mediating; Mentorship; Modeling; N-Methyl-D-Aspartate Receptors; Neurons; Play; Preparation; Regulation; Research; Rewards; Rodent; Series; Societies; Stress; Synapses; Testing; Training; alcohol exposure; alcohol use disorder; behavioral response; brain circuitry; career development; ex vivo imaging; experience; experimental study; new therapeutic target; posters; postsynaptic; receptor function; recruit; skills; symposium; therapeutic development

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.

抽象的 酒精使用障碍（AUD）是我们社会的巨大健康和财务燃烧。越来越多的文学作品 表明扩展的杏仁核在应力奖励相互作用中起关键作用，这可能介导关键 对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 向上调节谷氨酸释放的CRF受体依赖性增强以及突触后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“两击”模型， 慢性酒精暴露和戒断产生的情感中断取决于 扩展杏仁核突触的协调前和突触后调节。为了增强这一点 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 可以通过更改来组织和招募谷氨酸输入到BNST（来自岛的） 这些细胞上的兴奋性和抑制作用。她将在强制节制模型中探索这些机制 长期暴露于慢性酒精，获得体内成像和电生理训练以及经验 啮齿动物酒精暴露模型。指导还将通过手稿专注于沟通技巧 为科学会议准备海报的准备和准备。