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Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area

Understanding the neural mechanisms underlying sleep state transitions is a fundamental goal of neurobiology and important for the development of new treatments for insomnia and other sleep disorders. Yet, brain circuits controlling this process remain poorly understood. Here we identify a populatio...

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Autores principales: Teng, Sasa, Zhen, Fenghua, Wang, Li, Schalchli, Jose Canovas, Simko, Jane, Chen, Xinyue, Jin, Hao, Makinson, Christopher D., Peng, Yueqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374761/
https://www.ncbi.nlm.nih.gov/pubmed/35961989
http://dx.doi.org/10.1038/s41467-022-32461-3
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author Teng, Sasa
Zhen, Fenghua
Wang, Li
Schalchli, Jose Canovas
Simko, Jane
Chen, Xinyue
Jin, Hao
Makinson, Christopher D.
Peng, Yueqing
author_facet Teng, Sasa
Zhen, Fenghua
Wang, Li
Schalchli, Jose Canovas
Simko, Jane
Chen, Xinyue
Jin, Hao
Makinson, Christopher D.
Peng, Yueqing
author_sort Teng, Sasa
collection PubMed
description Understanding the neural mechanisms underlying sleep state transitions is a fundamental goal of neurobiology and important for the development of new treatments for insomnia and other sleep disorders. Yet, brain circuits controlling this process remain poorly understood. Here we identify a population of sleep-active glutamatergic neurons in the ventrolateral medulla (VLM) that project to the preoptic area (POA), a prominent sleep-promoting region, in mice. Microendoscopic calcium imaging demonstrate that these VLM glutamatergic neurons display increased activity during the transitions from wakefulness to Non-Rapid Eye Movement (NREM) sleep. Chemogenetic silencing of POA-projecting VLM neurons suppresses NREM sleep, whereas chemogenetic activation of these neurons promotes NREM sleep. Moreover, we show that optogenetic activation of VLM glutamatergic neurons or their projections in the POA initiates NREM sleep in awake mice. Together, our findings uncover an excitatory brainstem-hypothalamic circuit that controls the wake-sleep transitions.
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spelling pubmed-93747612022-08-14 Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area Teng, Sasa Zhen, Fenghua Wang, Li Schalchli, Jose Canovas Simko, Jane Chen, Xinyue Jin, Hao Makinson, Christopher D. Peng, Yueqing Nat Commun Article Understanding the neural mechanisms underlying sleep state transitions is a fundamental goal of neurobiology and important for the development of new treatments for insomnia and other sleep disorders. Yet, brain circuits controlling this process remain poorly understood. Here we identify a population of sleep-active glutamatergic neurons in the ventrolateral medulla (VLM) that project to the preoptic area (POA), a prominent sleep-promoting region, in mice. Microendoscopic calcium imaging demonstrate that these VLM glutamatergic neurons display increased activity during the transitions from wakefulness to Non-Rapid Eye Movement (NREM) sleep. Chemogenetic silencing of POA-projecting VLM neurons suppresses NREM sleep, whereas chemogenetic activation of these neurons promotes NREM sleep. Moreover, we show that optogenetic activation of VLM glutamatergic neurons or their projections in the POA initiates NREM sleep in awake mice. Together, our findings uncover an excitatory brainstem-hypothalamic circuit that controls the wake-sleep transitions. Nature Publishing Group UK 2022-08-12 /pmc/articles/PMC9374761/ /pubmed/35961989 http://dx.doi.org/10.1038/s41467-022-32461-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Teng, Sasa
Zhen, Fenghua
Wang, Li
Schalchli, Jose Canovas
Simko, Jane
Chen, Xinyue
Jin, Hao
Makinson, Christopher D.
Peng, Yueqing
Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area
title Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area
title_full Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area
title_fullStr Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area
title_full_unstemmed Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area
title_short Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area
title_sort control of non-rem sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374761/
https://www.ncbi.nlm.nih.gov/pubmed/35961989
http://dx.doi.org/10.1038/s41467-022-32461-3
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