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

项目摘要 我们请求行政副刊PA-20-272；NOT-OD-20-055：“特别利益通知(NOSI)： 首次获奖者生物医学和行为研究连续性行政补充资料 美国国立卫生研究院研究项目资助奖。由于PI的关键生活事件，要求补充 他的第二个孩子出生了。需要额外的资金来支持一名兼职博士后助理，他将 进行全细胞膜片钳电生理实验，分析数据，传播研究 通过手稿和会议演示的研究结果。这位同事将对我们的实验室返回到 在PI的关键人生事件之后，我们的预期生产力水平。 原定目标不变： 目的1(K99)：验证mGlu1和mGlu5调节可以改善特定性别酒精的假设。 通过对PFC PV-INS的作用诱导病理生理学。PV-IN突触的生理学和可塑性 在体外切片准备过程中被审问。此外，还将用纤维在体内检测PV-IN的功能 当雌性和雄性小鼠寻求酒精并执行其他PFC依赖行为时，进行光度测量。 目标2(R00)：检验性别特定的酒精引起的不同PFC输出的失调可以 通过mGlu1和mGlu5的抑制传递得到修复。将使用病毒式方法来 基于投射靶点的PFC锥体细胞在雌性和雄性转基因光遗传小鼠中的标记 ChR2)。我们将评估PV-INS如何控制间歇性酒精后特定的PFC输出通路 以及性别和mGlu1/mGlu5是如何调节这些现象的。

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.