脑干蓝斑核团调控卵巢功能的神经环路机制

目标：解析脑干蓝斑核团在正常及压力应激条件下调控卵巢功能的神经环路机制。我们的前期实验发现：位于脑干的压力应激关键核团蓝斑与卵巢存在多级跨突触的神经结构连接；且蓝斑的光遗传学激活直接导致卵巢功能紊乱。本研究将利用野生型及转基因小鼠建立压力应激模型，跨领域交叉利用光遗传学、药物遗传学、在体光纤钙成像、多通道电生理记录、单细胞测序、神经环路示踪等技术，结合卵巢功能检测，包括动物发情周期、性腺激素分泌、卵泡发育、排卵等，研究：（1）蓝斑-卵巢的神经环路结构；（2）探索蓝斑-卵巢通路与经典的下丘脑-垂体-卵巢轴的关联；（3）筛选卵巢功能调控的外周神经递质及受体靶点。本项目将有助于我们理解卵巢神经支配的中枢调控机制，为压力应激相关卵巢疾病的致病机理及治疗靶点的探索提供新的理论依据和坚实的实验基础，具有理论、临床的重要意义。

This project aims to decipher the regulation of ovarian function by locus coeruleus (LC) and its underlying neural circuitry. Our previous work finds that: (1) LC projects to ovary through trans-synaptic connection. (2) optogenetic activation of LC impairs ovarian function. We will use WT and transgenic mice to set up acute and chronic stress model. This together with state of art neural circuitry technologies like optogenetics, chemogenetics, free-moving fiber optometry, multi-channel electrophysiology, single-cell sequencing, and viral tracing will be used to study the regulation of ovarian functions (steroidogenesis, follicular development and ovulation). We will study (1) the anatomical structure of LC-ovary pathway, (2) the relationship between LC-ovary pathway and the classical HPG axis, (3) the neurotransmitter and its receptor for peripheral ovarian regulation. The project will investigate the central control of ovarian function through direct nerve innervation and provide a new theoretical and experimental basis for the exploration of the pathogenesis and therapeutic targets of stress-related ovarian diseases.