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

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.

Automated summary

Information transfer within neuronal circuits depends on the balance and recurrent activity of excitatory and inhibitory neurotransmission. Astrocytes, a type of glial cell, act as a dynamic Cl- reservoir regulating Cl- homeostasis in the central nervous system (CNS). Intracellular chloride concentration in astrocytes is higher and more stable during sleep, while it is lower and fluctuates in response to sensory input and motor activity during wakefulness. Efflux of Cl- from astrocytes supports inhibitory transmission in the CNS.