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

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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.

Original languageEnglish
Article number1871
JournalNature Communications
Issue number1
Number of pages14
Publication statusPublished - 2023

Bibliographical note

© 2023. The Author(s).

    Research areas

  • Mice, Animals, Astrocytes/physiology, Chlorides, Synaptic Transmission, Neuroglia, Brain

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