Prefrontal synaptic regulation of homeostatic sleep pressure revealed through synaptic chemogenetics.

Autor: Sawada T; International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.; Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Iino Y; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Yoshida K; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.; RIKEN Center for Brain Science, Wako, Saitama, Japan., Okazaki H; International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.; Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Nomura S; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.; Department of Physiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Shimizu C; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Arima T; International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.; Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.; Department of Physiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Juichi M; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan., Zhou S; International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Kurabayashi N; Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan., Sakurai T; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.; Department of Molecular Behavioral Physiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan., Yagishita S; International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.; Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Yanagisawa M; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Toyoizumi T; RIKEN Center for Brain Science, Wako, Saitama, Japan.; Department of Mathematical Informatics, Graduate School of Information Science and Technology, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Kasai H; International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.; Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Shi S; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Sep 27; Vol. 385 (6716), pp. 1459-1465. Date of Electronic Publication: 2024 Sep 26.
DOI: 10.1126/science.adl3043
Abstrakt: 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.
Databáze: MEDLINE
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