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GABA tone regulation and its cognitive functions in the brainHighly Cited Paper

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Title
GABA tone regulation and its cognitive functions in the brain
Author(s)
Wuhyun Koh; Kwak, Hankyul; Cheong, Eunji; C. Justin Lee
Publication Date
2023-09
Journal
Nature Reviews Neuroscience, v.24, no.9, pp.523 - 539
Publisher
Springer Nature
Abstract
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter released at GABAergic synapses, mediating fast-acting phasic inhibition. Emerging lines of evidence unequivocally indicate that a small amount of extracellular GABA — GABA tone — exists in the brain and induces a tonic GABA current that controls neuronal activity on a slow timescale relative to that of phasic inhibition. Surprisingly, studies indicate that glial cells that synthesize GABA, such as astrocytes, release GABA through non-vesicular mechanisms, such as channel-mediated release, and thereby act as the source of GABA tone in the brain. In this Review, we first provide an overview of major advances in our understanding of the cell-specific molecular and cellular mechanisms of GABA synthesis, release and clearance that regulate GABA tone in various brain regions. We next examine the diverse ways in which the tonic GABA current regulates synaptic transmission and synaptic plasticity through extrasynaptic GABAA-receptor-mediated mechanisms. Last, we discuss the physiological mechanisms through which tonic inhibition modulates cognitive function on a slow timescale. In this Review, we emphasize that the cognitive functions of tonic GABA current extend beyond mere inhibition, laying a foundation for future research on the physiological and pathophysiological roles of GABA tone regulation in normal and abnormal psychiatric conditions. © 2023, Springer Nature Limited.
URI
https://pr.ibs.re.kr/handle/8788114/13913
DOI
10.1038/s41583-023-00724-7
ISSN
1471-003X
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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