Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice
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Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice. / 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; Nedergaard, Maiken.
In: Nature Communications, Vol. 14, No. 1, 1871, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice
AU - Untiet, Verena
AU - Beinlich, Felix R M
AU - Kusk, Peter
AU - Kang, Ning
AU - Ladrón-de-Guevara, Antonio
AU - Song, Wei
AU - Kjaerby, Celia
AU - Andersen, Mie
AU - Hauglund, Natalie
AU - Bojarowska, Zuzanna
AU - Sigurdsson, Björn
AU - Deng, Saiyue
AU - Hirase, Hajime
AU - Petersen, Nicolas C
AU - Verkhratsky, Alexei
AU - Nedergaard, Maiken
N1 - © 2023. The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Mice
KW - Animals
KW - Astrocytes/physiology
KW - Chlorides
KW - Synaptic Transmission
KW - Neuroglia
KW - Brain
U2 - 10.1038/s41467-023-37433-9
DO - 10.1038/s41467-023-37433-9
M3 - Journal article
C2 - 37015909
VL - 14
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1871
ER -
ID: 345509445