Prefrontal synaptic regulation of homeostatic sleep pressure revealed through synaptic chemogenetics

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.

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Publication Details

Journal
Science
Published
2024-09-26
DOI
https://doi.org/10.1126/science.adl3043
Citations
32
Primary Topic
Sleep and Wakefulness Research
Type
article
Field-Weighted Citation Impact
10.97
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article

Prefrontal synaptic regulation of homeostatic sleep pressure revealed through synaptic chemogenetics

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32 citations
Science
Sleep and Wakefulness Research
10.97
article

Prefrontal synaptic regulation of homeostatic sleep pressure revealed through synaptic chemogenetics

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

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.

ScienceVol. 385(6716)
University of Tsukuba (JP), RIKEN Center for Brain Science (JP), Tokyo Metropolitan Institute of Medical Science (JP), The University of Tokyo (JP), The University of Texas Southwestern Medical Center (US), Tsukuba International University (JP)
Openalex Percentile: Top 1%
Sleep and Wakefulness Research
10.97
DOISourceOpenAlex
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