1. Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice.
- Author
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Untiet, Verena, Beinlich, Felix R. M., Kusk, Peter, Kang, Ning, Ladrón-de-Guevara, Antonio, Song, Wei, Kjaerby, Celia, Andersen, Mie, Hauglund, Natalie, Bojarowska, Zuzanna, Sigurdsson, Björn, Deng, Saiyue, Hirase, Hajime, Petersen, Nicolas C., Verkhratsky, Alexei, and Nedergaard, Maiken
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NEURAL transmission ,CENTRAL nervous system ,NEUROGLIA ,CHLORIDES ,MICE ,ASTROCYTES - 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. Astrocytes act as a dynamic Cl− reservoir regulating Cl− homeostasis in the CNS. Astrocytic Cl− is high and stable during sleep, it is lower during wakefulness and fluctuates in response to sensory input and motor activity. Efflux of Cl− from astrocytes supports inhibitory transmission in the CNS. [ABSTRACT FROM AUTHOR]- Published
- 2023
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