主讲人：姚骏实验室代表 陈运

时间：2021年8月17日（周二）下午 12:30-13:30

与会方式：扫描下方二维码填写报名问卷

主办单位：清华IDG麦戈文脑科学研究院

讲座简介：Synaptic vesicle (SV) docking is a dynamic multi-stage process that is required for efficient neurotransmitter release in response to nerve impulses. Although the steady-state SV docking likely involves the cooperation of Synaptotagmin-1 (Syt1) and SNAREs, where and how the docking process is initiated remains unknown. PI(4,5)P2 can interact with Syt1 and SNAREs to contribute to vesicle exocytosis. In the present study, using the CRISPRi-mediated multiplex gene knockdown and 3-D electron tomography approaches, we showed that in mouse hippocampal synapses, SV docking was initiated at ~12 nm to the active zone (AZ) by Syt1. Furthermore, we demonstrated that PI(4,5)P2 was the membrane partner of Syt1 to initiate SV docking, and disrupting their interaction could abolish the docking initiation. In contrast, the SNARE complex only contributed to the tight SV docking within 0-2 nm. Therefore, Syt1 interacted with PI(4,5)P2 to loosely dock SVs within 2-12 nm to the AZ in hippocampal neurons.

课题组简介：姚骏，清华-IDG/麦戈文脑科学研究院、清华大学生命科学学院、清华—北大生命科学联合中心研究员。课题组致力于从遗传学、分子和神经环路等多个维度阐明情感障碍（双相情感障碍和抑郁症）的发病机理。情感障碍是发病率、遗传率和自杀率最高的一类疾病，但目前该类疾病的发病机理仍不清楚，临床药物也存在很多限制和副作用。课题组主要研究的是基于多能干细胞(iPSC)、3D类脑和小鼠模型，采用膜片钳和在体电生理、超高分辨率显微成像、动物行为学、光遗传、冷冻电镜以及多种基因测序手段，从病人iPSC分化的神经元和3D类脑中遴选出疑似与发病相关的关键基因或分子通路，结合类脑和小鼠模型探究：1）该通路导致疾病发生的分子水平机理；2）产生致病影响的小鼠关键脑区和神经环路；3）在人类神经元中受不同易感基因调控的遗传学机制。

图1.姚骏博士、研究员

图2.与会二维码