A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy
Abstract Physiological rapid eye movement (REM) sleep termination is vital for initiating non-REM (NREM) sleep or arousal, whereas the suppression of excessive REM sleep is promising in treating narcolepsy. However, the neuronal mechanisms controlling REM sleep termination and keeping sleep continua...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-10-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-022-00456-5 |
| _version_ | 1811257146365444096 |
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| author | Ze-Ka Chen Hui Dong Cheng-Wei Liu Wen-Ying Liu Ya-Nan Zhao Wei Xu Xiao Sun Yan-Yu Xiong Yuan-Yuan Liu Xiang-Shan Yuan Bing Wang Michael Lazarus Yoan Chérasse Ya-Dong Li Fang Han Wei-Min Qu Feng-Fei Ding Zhi-Li Huang |
| author_facet | Ze-Ka Chen Hui Dong Cheng-Wei Liu Wen-Ying Liu Ya-Nan Zhao Wei Xu Xiao Sun Yan-Yu Xiong Yuan-Yuan Liu Xiang-Shan Yuan Bing Wang Michael Lazarus Yoan Chérasse Ya-Dong Li Fang Han Wei-Min Qu Feng-Fei Ding Zhi-Li Huang |
| author_sort | Ze-Ka Chen |
| collection | DOAJ |
| description | Abstract Physiological rapid eye movement (REM) sleep termination is vital for initiating non-REM (NREM) sleep or arousal, whereas the suppression of excessive REM sleep is promising in treating narcolepsy. However, the neuronal mechanisms controlling REM sleep termination and keeping sleep continuation remain largely unknown. Here, we reveal a key brainstem region of GABAergic neurons in the control of both physiological REM sleep and cataplexy. Using fiber photometry and optic tetrode recording, we characterized the dorsal part of the deep mesencephalic nucleus (dDpMe) GABAergic neurons as REM relatively inactive and two different firing patterns under spontaneous sleep–wake cycles. Next, we investigated the roles of dDpMe GABAergic neuronal circuits in brain state regulation using optogenetics, RNA interference technology, and celltype-specific lesion. Physiologically, dDpMe GABAergic neurons causally suppressed REM sleep and promoted NREM sleep through the sublaterodorsal nucleus and lateral hypothalamus. In-depth studies of neural circuits revealed that sublaterodorsal nucleus glutamatergic neurons were essential for REM sleep termination by dDpMe GABAergic neurons. In addition, dDpMe GABAergic neurons efficiently suppressed cataplexy in a rodent model. Our results demonstrated that dDpMe GABAergic neurons controlled REM sleep termination along with REM/NREM transitions and represented a novel potential target to treat narcolepsy. |
| first_indexed | 2024-04-12T17:52:48Z |
| format | Article |
| id | doaj.art-7ab8b4c0d7e84170a9272b6c8bcffd23 |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-04-12T17:52:48Z |
| publishDate | 2022-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-7ab8b4c0d7e84170a9272b6c8bcffd232022-12-22T03:22:27ZengNature Publishing GroupCell Discovery2056-59682022-10-018111510.1038/s41421-022-00456-5A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexyZe-Ka Chen0Hui Dong1Cheng-Wei Liu2Wen-Ying Liu3Ya-Nan Zhao4Wei Xu5Xiao Sun6Yan-Yu Xiong7Yuan-Yuan Liu8Xiang-Shan Yuan9Bing Wang10Michael Lazarus11Yoan Chérasse12Ya-Dong Li13Fang Han14Wei-Min Qu15Feng-Fei Ding16Zhi-Li Huang17Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan UniversityENT Institute and Otorhinolaryngology Department, Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan UniversityInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of TsukubaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of TsukubaDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversitySleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People’s HospitalDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityAbstract Physiological rapid eye movement (REM) sleep termination is vital for initiating non-REM (NREM) sleep or arousal, whereas the suppression of excessive REM sleep is promising in treating narcolepsy. However, the neuronal mechanisms controlling REM sleep termination and keeping sleep continuation remain largely unknown. Here, we reveal a key brainstem region of GABAergic neurons in the control of both physiological REM sleep and cataplexy. Using fiber photometry and optic tetrode recording, we characterized the dorsal part of the deep mesencephalic nucleus (dDpMe) GABAergic neurons as REM relatively inactive and two different firing patterns under spontaneous sleep–wake cycles. Next, we investigated the roles of dDpMe GABAergic neuronal circuits in brain state regulation using optogenetics, RNA interference technology, and celltype-specific lesion. Physiologically, dDpMe GABAergic neurons causally suppressed REM sleep and promoted NREM sleep through the sublaterodorsal nucleus and lateral hypothalamus. In-depth studies of neural circuits revealed that sublaterodorsal nucleus glutamatergic neurons were essential for REM sleep termination by dDpMe GABAergic neurons. In addition, dDpMe GABAergic neurons efficiently suppressed cataplexy in a rodent model. Our results demonstrated that dDpMe GABAergic neurons controlled REM sleep termination along with REM/NREM transitions and represented a novel potential target to treat narcolepsy.https://doi.org/10.1038/s41421-022-00456-5 |
| spellingShingle | Ze-Ka Chen Hui Dong Cheng-Wei Liu Wen-Ying Liu Ya-Nan Zhao Wei Xu Xiao Sun Yan-Yu Xiong Yuan-Yuan Liu Xiang-Shan Yuan Bing Wang Michael Lazarus Yoan Chérasse Ya-Dong Li Fang Han Wei-Min Qu Feng-Fei Ding Zhi-Li Huang A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy Cell Discovery |
| title | A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy |
| title_full | A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy |
| title_fullStr | A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy |
| title_full_unstemmed | A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy |
| title_short | A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy |
| title_sort | cluster of mesopontine gabaergic neurons suppresses rem sleep and curbs cataplexy |
| url | https://doi.org/10.1038/s41421-022-00456-5 |
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