A pontine-medullary loop crucial for REM sleep and its deficit in Parkinson’s disease
Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp<sup>+</sup> neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp<sup>+</sup> neurons, neurons expressing nitric oxide synthase 1 (Nos1<sup>+</sup> neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit. Nos1<sup>+</sup> neurons also project to areas that control wide forebrain activity. Ablating Crhbp<sup>+</sup> neurons reduces sleep and impairs REM sleep atonia. In Parkinson's disease patients with REM sleep behavior disorders, CRHBP-immunoreactive neurons are largely reduced and contain pathologic α-synuclein, providing insight into the mechanisms underlying the sleep deficits characterizing this disease.
Authors
- Goichi Beck (ORCID: https://orcid.org/0000-0001-8890-2743)
- Masashi Yanagisawa (ORCID: https://orcid.org/0000-0002-7358-4022)
- Mika Kanuka
- Marina Takagi
- Yuki Saito (ORCID: https://orcid.org/0000-0002-2297-7205)
- Shigeo Murayama (ORCID: https://orcid.org/0000-0001-9709-5242)
- Yu Hayashi (ORCID: https://orcid.org/0000-0001-5007-4532)
- Masanori Sakaguchi (ORCID: https://orcid.org/0000-0002-7211-9452)
- Masashi Ikuno (ORCID: https://orcid.org/0000-0002-3306-7039)
- Hodaka Yamakado
- Yo Oishi (ORCID: https://orcid.org/0000-0002-7363-0594)
- Kaeko Tanaka
- Yoshifumi Arai (ORCID: https://orcid.org/0000-0003-1496-7610)
- Hideki Mochizuki (ORCID: https://orcid.org/0000-0002-2270-7109)
- Yoshimi Nakagawa (ORCID: https://orcid.org/0000-0001-8710-5232)
- Kousuke Baba
- Kazuya Sakai (ORCID: https://orcid.org/0000-0001-9618-581X)
- Chika Tatsuzawa
- Masahiko Watanabe (ORCID: https://orcid.org/0000-0001-5037-7138)
- Takeshi Sakurai (ORCID: https://orcid.org/0000-0002-3533-0750)
- Mitsuaki Kashiwagi
- Ryosuke Takahashi
- Yumiko Koga
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Centre National de la Recherche Scientifique (FR)
- University of Tsukuba (JP)
- Inserm (FR)
- Hokkaido University (JP)
- Kyoto University (JP)
- Toyama College (JP)
- Centre de Recherche en Neurosciences de Lyon (FR)
- University of Toyama (JP)
- The University of Tokyo (JP)
- The University of Osaka (JP)
- Tsukuba International University (JP)
Publication Details
- Journal
- Cell
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1016/j.cell.2024.08.046
- Citations
- 32
- Primary Topic
- Sleep and Wakefulness Research
- Type
- article
- Field-Weighted Citation Impact
- 10.97
Funders
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science