Adenosine-independent regulation of the sleep–wake cycle by astrocyte activity

Abstract Astrocytes play a crucial role in regulating sleep–wake behavior, and adenosine signaling is generally thought to be involved. Here we show multiple lines of evidence supporting that modulation of the sleep–wake behavior by astrocyte Ca2+ activity could occur without adenosine signaling. In...

Full description

Bibliographic Details
Main Authors: Wanling Peng, Xiaotong Liu, Guofen Ma, Zhaofa Wu, Ziyue Wang, Xiang Fei, Meiling Qin, Lizhao Wang, Yulong Li, Siyu Zhang, Min Xu
Format: Article
Language:English
Published: Nature Publishing Group 2023-02-01
Series:Cell Discovery
Online Access:https://doi.org/10.1038/s41421-022-00498-9
_version_ 1811166074072203264
author Wanling Peng
Xiaotong Liu
Guofen Ma
Zhaofa Wu
Ziyue Wang
Xiang Fei
Meiling Qin
Lizhao Wang
Yulong Li
Siyu Zhang
Min Xu
author_facet Wanling Peng
Xiaotong Liu
Guofen Ma
Zhaofa Wu
Ziyue Wang
Xiang Fei
Meiling Qin
Lizhao Wang
Yulong Li
Siyu Zhang
Min Xu
author_sort Wanling Peng
collection DOAJ
description Abstract Astrocytes play a crucial role in regulating sleep–wake behavior, and adenosine signaling is generally thought to be involved. Here we show multiple lines of evidence supporting that modulation of the sleep–wake behavior by astrocyte Ca2+ activity could occur without adenosine signaling. In the basal forebrain and the brainstem, two brain regions that are known to be essential for sleep–wake regulation, chemogenetically-induced astrocyte Ca2+ elevation significantly modulated the sleep–wake cycle. Although astrocyte Ca2+ level positively correlated with the amount of extracellular adenosine, as revealed by a genetically encoded adenosine sensor, we found no detectable change in adenosine level after suppressing astrocyte Ca2+ elevation, and transgenic mice lacking one of the major extracellular ATP-adenosine conversion enzymes showed similar extracellular adenosine level and astrocyte Ca2+-induced sleep modulation. Furthermore, astrocyte Ca2+ is dependent primarily on local neuronal activity, causing brain region-specific regulation of the sleep–wake cycle. Thus, neural activity-dependent astrocyte activity could regulate the sleep–wake behavior independent of adenosine signaling.
first_indexed 2024-04-10T15:46:36Z
format Article
id doaj.art-9c675df3ac1a4b12b29bd9596c539343
institution Directory Open Access Journal
issn 2056-5968
language English
last_indexed 2024-04-10T15:46:36Z
publishDate 2023-02-01
publisher Nature Publishing Group
record_format Article
series Cell Discovery
spelling doaj.art-9c675df3ac1a4b12b29bd9596c5393432023-02-12T12:04:24ZengNature Publishing GroupCell Discovery2056-59682023-02-019112510.1038/s41421-022-00498-9Adenosine-independent regulation of the sleep–wake cycle by astrocyte activityWanling Peng0Xiaotong Liu1Guofen Ma2Zhaofa Wu3Ziyue Wang4Xiang Fei5Meiling Qin6Lizhao Wang7Yulong Li8Siyu Zhang9Min Xu10Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesCenter for Brain Science of Shanghai Children’s Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Membrane Biology, Peking University School of Life SciencesCenter for Brain Science of Shanghai Children’s Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of MedicineInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesCenter for Brain Science of Shanghai Children’s Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Membrane Biology, Peking University School of Life SciencesCenter for Brain Science of Shanghai Children’s Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of MedicineInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of SciencesAbstract Astrocytes play a crucial role in regulating sleep–wake behavior, and adenosine signaling is generally thought to be involved. Here we show multiple lines of evidence supporting that modulation of the sleep–wake behavior by astrocyte Ca2+ activity could occur without adenosine signaling. In the basal forebrain and the brainstem, two brain regions that are known to be essential for sleep–wake regulation, chemogenetically-induced astrocyte Ca2+ elevation significantly modulated the sleep–wake cycle. Although astrocyte Ca2+ level positively correlated with the amount of extracellular adenosine, as revealed by a genetically encoded adenosine sensor, we found no detectable change in adenosine level after suppressing astrocyte Ca2+ elevation, and transgenic mice lacking one of the major extracellular ATP-adenosine conversion enzymes showed similar extracellular adenosine level and astrocyte Ca2+-induced sleep modulation. Furthermore, astrocyte Ca2+ is dependent primarily on local neuronal activity, causing brain region-specific regulation of the sleep–wake cycle. Thus, neural activity-dependent astrocyte activity could regulate the sleep–wake behavior independent of adenosine signaling.https://doi.org/10.1038/s41421-022-00498-9
spellingShingle Wanling Peng
Xiaotong Liu
Guofen Ma
Zhaofa Wu
Ziyue Wang
Xiang Fei
Meiling Qin
Lizhao Wang
Yulong Li
Siyu Zhang
Min Xu
Adenosine-independent regulation of the sleep–wake cycle by astrocyte activity
Cell Discovery
title Adenosine-independent regulation of the sleep–wake cycle by astrocyte activity
title_full Adenosine-independent regulation of the sleep–wake cycle by astrocyte activity
title_fullStr Adenosine-independent regulation of the sleep–wake cycle by astrocyte activity
title_full_unstemmed Adenosine-independent regulation of the sleep–wake cycle by astrocyte activity
title_short Adenosine-independent regulation of the sleep–wake cycle by astrocyte activity
title_sort adenosine independent regulation of the sleep wake cycle by astrocyte activity
url https://doi.org/10.1038/s41421-022-00498-9
work_keys_str_mv AT wanlingpeng adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT xiaotongliu adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT guofenma adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT zhaofawu adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT ziyuewang adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT xiangfei adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT meilingqin adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT lizhaowang adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT yulongli adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT siyuzhang adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity
AT minxu adenosineindependentregulationofthesleepwakecyclebyastrocyteactivity