时间: 14:00-15:30 on Tues.,Mar.18, 2025

地点：医学科学楼B323会议室

主讲人: Dr. Qinghua Liu

主持人: Dr. Yi Lin

题目: A mechanistic link between synaptic function and sleep regulation in mice

摘要：

Recent studies have identified multiple sleep-promoting protein kinases, including the AMPK-related protein kinase SIK3. Phosphoproteomics analysis of Sleepy (Sik3^Slp) and sleep-deprived wild-type mouse brains, two opposite models of high sleep need, reveals a potential link between synaptic protein phosphorylation and sleep need regulation. However, the causal relationship between synaptic function and sleep regulation are not fully explored. Here, we applied the AAV-mediated adult brain chimeric (ABC)-expression or knockout system to systematically screen pre- and post-synaptic proteins and identified several novel regulators of the amount and intensity of non-rapid eye movement (NREM) sleep. Our results are consistent with the idea that reduced synaptic transmission is linked to hypersomnia, whereas enhanced synaptic transmission leads to insomnia. Moreover, we used analog-specific (AS) kinase to identify the candidate substrates of SLP/SIK3 kinase in the mouse brain, which included many synaptic proteins. Cryo-EM imaging and electrophysiology recording revealed morphological changes of synapses and reduced frequency of miniature excitatory postsynaptic currents (mEPSCs) in the hippocampal neurons of Sleepy mice. Furthermore, ABC-expression of constitutively active syntaxin-1a (pre-synaptic) or DLGAP3 (post-synaptic) in the mouse brain neurons rescued both mEPSC frequency and hypersomnia of Sleepy mice. Together, these results indicate that specific synaptic proteins function as downstream effectors of sleep regulation and provide direct evidence supporting a mechanistic link between synaptic function and sleep regulation in mice. 

简介：

刘清华研究员1992年毕业于武汉大学，2000年于美国贝勒医学院获得博士学位，随后在美国德州大学西南医学中心王晓东院士实验室进行博士后训练，2004-2017年任美国德州大学西南医学中心助理教授到终身副教授，2013-2021年兼职日本筑波大学国际综合睡眠医学研究所教授，2018年-至今担任北京生命科学研究所资深研究员。刘清华教授曾在核酸干扰和小RNA的研究领域取得了卓越的成就，近十年来跨跃到神经科学领域，在睡眠和恐惧调控的分子遗传机制方面颇有建树，开展了首个先天性恐惧的大规模正向遗传学筛选，创立高通量小鼠体细胞遗传学睡眠筛选平台，发现转录调控睡眠时长的首个信号通路，并揭示突触蛋白磷酸化与睡眠调节机制的紧密联系。曾获美国达蒙.鲁尼恩博士后奖学金（2001），“特克斯”蒙克利夫生物医学研究荣誉学者（2004），达蒙.鲁尼恩学者奖（2005），北京市海聚工程特聘全职专家（2018），新基石研究员（2024）。