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Researchers from University of Tsukuba elucidated the neural circuit that induces rapid eye movement (REM) sleep, a stage during which we actively dream. They also discovered that abnormalities in the neurons constituting this circuit lead to REM sleep behavior disorder, a condition in which the body moves based on dreams during REM sleep.

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)