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Researchers from University of Tsukuba investigated the mechanisms that maintain the consistency of daily sleep quantity and quality. They developed a molecular tool that enhances synaptic connections between neurons in the mouse brain and created a mathematical model to predict the relationship between synapses and brain activity. Their study revealed that sleep is initiated when synaptic connections in the frontal cortex are strengthened and that these connections weaken during sleep in mice.

Tsukuba, Japan—Sleep deprivation typically results in longer and deeper sleep, thereby maintaining overall sleep quantity and quality through homeostatic regulation. However, the specific mechanisms by which the brain monitors and controls sleep homeostasis remain unclear.

To address this, the researchers focused on synaptic connections between neurons. They developed a novel molecular tool, SYNCit-K, which enhances synaptic strength, and EIN (excitatory-inhibitory neuronal network) model, a mathematical framework predicting the relationship between synaptic strength and brain activity. Application of SYNCit-K to the frontal cortex of mice induced sleep, while inhibition of synaptic enhancement prevented the induction of deep sleep. Enhanced synaptic strength in the prefrontal cortex returned to normal levels following subsequent sleep. These findings aligned with predictions from the EIN model, elucidating how increased synaptic connections in the brain induce sleep.

Understanding the role of synaptic strength in sleep homeostasis offers potential for developing new therapeutic approaches to improve sleep quantity and quality. Moreover, expanding the application of SYNCit-K and the EIN model could advance the understanding of brain functions and the computational theories underlying sleep.

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This research was conducted as part of the World Premier International Research Center Initiative (WPI), JSPS KAKENHI grants, JST Strategic Basic Research Programs (CREST, ACT-X), JST-Mirai Program, AMED Moonshot Research and Development Program, AMED Brain/MINDS, and other research projects.

Original Paper

Title of original paper:

Prefrontal synaptic regulation of homeostatic sleep pressure revealed via synaptic chemogenetics

Journal:

Science

DOI:

10.1126/science.adl3043

Correspondence

Assistant Professor SHI Shoi
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba

Project Professor KASAI Haruo
International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo

Team Leader TOYOIZUMI Taro
RIKEN Center for Brain Science

Related Link

International Institute for Integrative Sleep Medicine (WPI-IIIS)