Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice

作者：Verena Untiet, Felix R. M. Beinlich, Peter Kusk, Ning Kang, Antonio Ladrón-de-Guevara, Wei Song, Celia Kjærby, Mie Andersen, Natalie Hauglund, Zuzanna Bojarowska, Björn Sigurðsson, Saiyue Deng, Hajime Hirase, N. Petersen, Alexei Verkhratsky, Maiken Nedergaard · 发表于：Nature Communications · 年份：2023 · DOI：10.1038/s41467-023-37433-9 · 被引用次数：71 · 研究领域：Neuroscience and Neuropharmacology Research、Sleep and Wakefulness Research、Photoreceptor and optogenetics research

Abstract Information transfer within neuronal circuits depends on the balance and recurrent activity of excitatory and inhibitory neurotransmission. Chloride (Cl − ) is the major central nervous system (CNS) anion mediating inhibitory neurotransmission. Astrocytes are key homoeostatic glial cells populating the CNS, although the role of these cells in regulating excitatory-inhibitory balance remains unexplored. Here we show that astrocytes act as a dynamic Cl − reservoir regulating Cl − homoeostasis in the CNS. We found that intracellular chloride concentration ([Cl − ] i ) in astrocytes is high and stable during sleep. In awake mice astrocytic [Cl − ] i is lower and exhibits large fluctuation in response to both sensory input and motor activity. Optogenetic manipulation of astrocytic [Cl − ] i directly modulates neuronal activity during locomotion or whisker stimulation. Astrocytes thus serve as a dynamic source of extracellular Cl − available for GABAergic transmission in awake mice, which represents a mechanism for modulation of the inhibitory tone during sustained neuronal activity.