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Sex differences in fast-spiking interneurons promote AUD-related PFC dysfunction: remediation by modulating mGlu1 and mGlu5 - Supplement Rev

快速峰值中间神经元的性别差异促进 AUD 相关的 PFC 功能障碍：通过调节 mGlu1 和 mGlu5 进行修复 - 补充修订版

基本信息

批准号：
10757096
负责人：
Max E Joffe
金额：
$ 7.95万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-08-31
项目状态：
已结题

项目摘要

Project Summary We are requesting administrative supplement PA-20-272; NOT-OD-20-055: “Notice of Special Interest (NOSI): Administrative Supplement for Continuity of Biomedical and Behavioral Research Among First-Time Recipients of NIH Research Project Grant Awards.” The supplement is requested due to a critical life event for the PI, the birth of his second child. Additional funds are needed to support a part-time postdoctoral associate who will perform the whole-cell patch-clamp electrophysiology experiments, analyze data, and disseminate study findings via manuscripts and conferences presentations. This associate will be essential in returning our lab to our expected levels of productivity following the PI’s critical life event. No Change to Original Aims: Aim 1 (K99): To test the hypothesis that mGlu1 and mGlu5 modulation can ameliorate sex-specific alcohol- induced pathophysiology through actions on PFC PV-INs. PV-IN synaptic physiology and plasticity will be interrogated in an ex vivo slice preparation. In addition, PV-IN function will be examined in vivo with fiber photometry while female and male mice seek alcohol and perform other PFC-dependent behaviors. Aim 2 (R00): To test the hypothesis that sex-specific alcohol-induced dysregulation of distinct PFC outputs can be remediated through mGlu1 and mGlu5 modulation of inhibitory transmission. A viral approach will be used to label PFC pyramidal cells based on projection target in female and male transgenic optogenetic mice (PV- ChR2). We will assess how PV-INs control specific PFC output pathways following intermittent alcohol exposure, and how these phenomena are regulated by sex and mGlu1/mGlu5.

项目摘要我们请求行政补充PA-20-272; NOT-OD-20-055：“特别关注通知（NOSI）：首次接受者生物医学和行为研究连续性的行政补充美国国立卫生研究院研究项目资助奖”由于主要研究者的重大生活事件，他的第二个孩子的出生。需要额外的资金来支持兼职博士后助理谁将进行全细胞膜片钳电生理实验，分析数据，并进行传播研究通过手稿和会议介绍得出的结论。这位助手将是我们实验室恢复我们在私家侦探的重大生活事件后的预期生产力水平。不改变原来的目标：目的1（K99）：为了验证mGlu 1和mGlu 5调节可以改善性别特异性酒精依赖的假设，通过对PFC PV-IN的作用诱导病理生理学。PV-IN突触生理学和可塑性将是在离体切片制备中询问。此外，将在体内用纤维检查PV-IN功能。当雌性和雄性小鼠寻找酒精并执行其他PFC依赖行为时，目的2（R 00）：检验性别特异性酒精诱导的不同PFC输出失调可以通过mGlu 1和mGlu 5调节抑制性传递来补救。将采用病毒式方法，在雌性和雄性转基因光遗传学小鼠（PV-1）中基于投射靶标记PFC锥体细胞 ChR2）。我们将评估间歇性饮酒后PV-IN如何控制特定的PFC输出途径暴露，以及这些现象是如何调节性别和mGlu 1/mGlu 5。