Elucidation of the neural circuitry inducing REM sleep and investigation of the cause of REM sleep behavior disorder

Tsukuba, Japan—During REM sleep, dreams are frequently seen. The induction of REM sleep was not well understood. Abnormalities in REM sleep precede various diseases. Notably, REM sleep behavior disorder, in which patients physically act out dreams by moving and vocalizing during REM sleep, has been noted as an early symptom of neurodegenerative diseases, such as Parkinson's disease. The cause of these abnormalities was unknown.

Herein, researchers identified two neuron types in the brainstem (pons and medulla oblongata) that induce REM sleep. These neurons form circuits connecting to brain regions that control cerebral cortex activation, rapid eye movement, and muscle tone loss, all characteristic of REM sleep. Artificial activation of this circuit strongly induces REM sleep, even in awake mice.

Moreover, inhibiting these REM sleep-inducing cells in mice led to abnormalities similar to those observed in patients with Parkinson's disease, such as body movements during REM sleep and a considerable reduction in REM sleep. Patients with Parkinson's disease and REM sleep behavior disorder had fewer REM sleep-inducing cells in the brainstem, revealing a cause of the disorder.

These findings are expected to enhance our understanding of REM sleep mechanisms and significance, aiding in the development of new prevention and treatment methods for sleep disorders and related diseases.

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This work was supported by the World Premier International Research Center Initiative (WPI), JSPS KAKENHI grant numbers JP20K22674, JP21K15179 (to M. Kashiwagi), and JP20K06910 (to G.B.); MEXT KAKENHI grant numbers JP23H04210, JP23H04668 (to Y.H.), JP16H06280 (to M.W.), and JP16H06277 (CoBiA) (to S.M.); and AMED grant numbers JP22gm1110008, JP21zf0127005 (to Y.H.), JP22wm0425018 (to G.B. and Y.H.), JP21dm0207070 (to H.M.), JP20dm017106, and JP21wm0425019 (to S.M.).

_{Original Paper}

Title of original paper:
A pontine-medullary loop crucial for REM sleep and its deficit in Parkinson's disease.

Journal:
Cell

DOI:
10.1016/j.cell.2024.08.046

_{Correspondence}

Visiting professor HAYASHI, Yu
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba / Professor, Department of Biological Sciences, Graduate School of Science, The University of Tokyo

Professor MOCHIZUKI, Hideki
Department of Neurology, Graduate School of Medicine, Osaka University

_{Related Link}

International Institute for Integrative Sleep Medicine (WPI-IIIS)

About the World Premier International Research Center Initiative (WPI)
The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).

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About International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba
World-class institute for sleep medicine, aiming to solve the mechanism of sleep/wakefulness by conducting basic to translational research
The mission of IIIS is to be a multidisciplinary, international hub for the research to elucidate the function of sleep and the fundamental mechanisms of sleep/wake regulation, to elucidate molecular pathogenesis of sleep disorders and related diseases, to develop preventive measures, diagnostic methods, and treatments for sleep.