Adenosine‐Dependent Arousal Induced by Astrocytes in a Brainstem Circuit

Abstract Astrocytes play a crucial role in regulating sleep‐wake behavior. However, how astrocytes govern a specific sleep‐arousal circuit remains unknown. Here, the authors show that parafacial zone (PZ) astrocytes responded to sleep‐wake cycles with state‐differential Ca2+ activity, peaking during...

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Main Authors: Yuwei Zhu, Jiale Ma, Yulan Li, Mengyang Gu, Xiang Feng, Yujin Shao, Lei Tan, Hui‐fang Lou, Li Sun, Yijun Liu, Ling‐hui Zeng, Zilong Qiu, Xiao‐ming Li, Shumin Duan, Yan‐qin Yu
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202407706
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author Yuwei Zhu
Jiale Ma
Yulan Li
Mengyang Gu
Xiang Feng
Yujin Shao
Lei Tan
Hui‐fang Lou
Li Sun
Yijun Liu
Ling‐hui Zeng
Zilong Qiu
Xiao‐ming Li
Shumin Duan
Yan‐qin Yu
author_facet Yuwei Zhu
Jiale Ma
Yulan Li
Mengyang Gu
Xiang Feng
Yujin Shao
Lei Tan
Hui‐fang Lou
Li Sun
Yijun Liu
Ling‐hui Zeng
Zilong Qiu
Xiao‐ming Li
Shumin Duan
Yan‐qin Yu
author_sort Yuwei Zhu
collection DOAJ
description Abstract Astrocytes play a crucial role in regulating sleep‐wake behavior. However, how astrocytes govern a specific sleep‐arousal circuit remains unknown. Here, the authors show that parafacial zone (PZ) astrocytes responded to sleep‐wake cycles with state‐differential Ca2+ activity, peaking during transitions from sleep to wakefulness. Using chemogenetic and optogenetic approaches, they find that activating PZ astrocytes elicited and sustained wakefulness by prolonging arousal episodes while impeding transitions from wakefulness to non‐rapid eye movement (NREM) sleep. Activation of PZ astrocytes specially induced the elevation of extracellular adenosine through the ATP hydrolysis pathway but not equilibrative nucleoside transporter (ENT) mediated transportation. Strikingly, the rise in adenosine levels induced arousal by activating A1 receptors, suggesting a distinct role for adenosine in the PZ beyond its conventional sleep homeostasis modulation observed in the basal forebrain (BF) and cortex. Moreover, at the circuit level, PZ astrocyte activation induced arousal by suppressing the GABA release from the PZGABA neurons, which promote NREM sleep and project to the parabrachial nucleus (PB). Thus, their study unveils a distinctive arousal‐promoting effect of astrocytes within the PZ through extracellular adenosine and elucidates the underlying mechanism at the neural circuit level.
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spelling doaj-art-1babe17ef69b46deade488e2c1c4a9c52025-08-20T02:43:28ZengWileyAdvanced Science2198-38442024-12-011148n/an/a10.1002/advs.202407706Adenosine‐Dependent Arousal Induced by Astrocytes in a Brainstem CircuitYuwei Zhu0Jiale Ma1Yulan Li2Mengyang Gu3Xiang Feng4Yujin Shao5Lei Tan6Hui‐fang Lou7Li Sun8Yijun Liu9Ling‐hui Zeng10Zilong Qiu11Xiao‐ming Li12Shumin Duan13Yan‐qin Yu14Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaKey Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine Hangzhou City University Hangzhou 310015 ChinaDepartment of Neurology Songjiang Hospital Songjiang Research Institute MOE‐Shanghai Key Laboratory for Children's Environmental Health Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaDepartment of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaAbstract Astrocytes play a crucial role in regulating sleep‐wake behavior. However, how astrocytes govern a specific sleep‐arousal circuit remains unknown. Here, the authors show that parafacial zone (PZ) astrocytes responded to sleep‐wake cycles with state‐differential Ca2+ activity, peaking during transitions from sleep to wakefulness. Using chemogenetic and optogenetic approaches, they find that activating PZ astrocytes elicited and sustained wakefulness by prolonging arousal episodes while impeding transitions from wakefulness to non‐rapid eye movement (NREM) sleep. Activation of PZ astrocytes specially induced the elevation of extracellular adenosine through the ATP hydrolysis pathway but not equilibrative nucleoside transporter (ENT) mediated transportation. Strikingly, the rise in adenosine levels induced arousal by activating A1 receptors, suggesting a distinct role for adenosine in the PZ beyond its conventional sleep homeostasis modulation observed in the basal forebrain (BF) and cortex. Moreover, at the circuit level, PZ astrocyte activation induced arousal by suppressing the GABA release from the PZGABA neurons, which promote NREM sleep and project to the parabrachial nucleus (PB). Thus, their study unveils a distinctive arousal‐promoting effect of astrocytes within the PZ through extracellular adenosine and elucidates the underlying mechanism at the neural circuit level.https://doi.org/10.1002/advs.202407706adenosinearousalastrocyteneural circuitparafacial zone
spellingShingle Yuwei Zhu
Jiale Ma
Yulan Li
Mengyang Gu
Xiang Feng
Yujin Shao
Lei Tan
Hui‐fang Lou
Li Sun
Yijun Liu
Ling‐hui Zeng
Zilong Qiu
Xiao‐ming Li
Shumin Duan
Yan‐qin Yu
Adenosine‐Dependent Arousal Induced by Astrocytes in a Brainstem Circuit
Advanced Science
adenosine
arousal
astrocyte
neural circuit
parafacial zone
title Adenosine‐Dependent Arousal Induced by Astrocytes in a Brainstem Circuit
title_full Adenosine‐Dependent Arousal Induced by Astrocytes in a Brainstem Circuit
title_fullStr Adenosine‐Dependent Arousal Induced by Astrocytes in a Brainstem Circuit
title_full_unstemmed Adenosine‐Dependent Arousal Induced by Astrocytes in a Brainstem Circuit
title_short Adenosine‐Dependent Arousal Induced by Astrocytes in a Brainstem Circuit
title_sort adenosine dependent arousal induced by astrocytes in a brainstem circuit
topic adenosine
arousal
astrocyte
neural circuit
parafacial zone
url https://doi.org/10.1002/advs.202407706
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