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突触化学遗传学揭示前额叶突触对稳态睡眠压力的调节
2024-09-28 12:39

日本筑波大学Shoi Shi等研究人员合作发现,突触化学遗传学揭示前额叶突触对稳态睡眠压力的调节。相关论文于2024年9月27日发表于国际学术期刊《科学》。

通过开发一个理论框架和一个分子工具来操控突触强度,研究人员探讨了细胞突触强度,与指示宏观睡眠压力的脑电图δ波功率之间的因果关系。数学模型预测,突触强度的增加促进神经元的“下状态”,并提高δ波功率。

该分子工具(突触靶向化学诱导转位的Kalirin-7,SYNCit-K)通过化学诱导转位蛋白Kalirin-7,引起树突棘的增大和突触的增强,进而证明前额叶皮层(PFC)兴奋性神经元的突触增强,增加了非快速眼动睡眠的数量和δ波功率。因此,PFC兴奋性神经元的突触强度决定了哺乳动物的睡眠压力。

据了解,睡眠由稳态过程调节,但在觉醒期间积累的睡眠压力的生物基础,触发睡眠并在睡眠期间消散,仍然难以捉摸。

附:英文原文

Title: Prefrontal synaptic regulation of homeostatic sleep pressure revealed through synaptic chemogenetics

Author: Takeshi Sawada, Yusuke Iino, Kensuke Yoshida, Hitoshi Okazaki, Shinnosuke Nomura, Chika Shimizu, Tomoki Arima, Motoki Juichi, Siqi Zhou, Nobuhiro Kurabayashi, Takeshi Sakurai, Sho Yagishita, Masashi Yanagisawa, Taro Toyoizumi, Haruo Kasai, Shoi Shi

Issue&Volume: 2024-09-27

Abstract: Sleep is regulated by homeostatic processes, yet the biological basis of sleep pressure that accumulates during wakefulness, triggers sleep, and dissipates during sleep remains elusive. We explored a causal relationship between cellular synaptic strength and electroencephalography delta power indicating macro-level sleep pressure by developing a theoretical framework and a molecular tool to manipulate synaptic strength. The mathematical model predicted that increased synaptic strength promotes the neuronal “down state” and raises the delta power. Our molecular tool (synapse-targeted chemically induced translocation of Kalirin-7, SYNCit-K), which induces dendritic spine enlargement and synaptic potentiation through chemically induced translocation of protein Kalirin-7, demonstrated that synaptic potentiation of excitatory neurons in the prefrontal cortex (PFC) increases nonrapid eye movement sleep amounts and delta power. Thus, synaptic strength of PFC excitatory neurons dictates sleep pressure in mammals.

DOI: adl3043

Source: https://www.science.org/doi/10.1126/science.adl3043

Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:63.714
官方网址:https://www.sciencemag.org/
投稿链接:https://cts.sciencemag.org/scc/#/login

本期文章: 《科学》:Volume 385 Issue 6716

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