2023-09-06 韓国基礎科学研究院(IBS)
◆アストロサイト(星状細胞)がGABAトーンの調節で主要な役割を果たし、トニックGABA電流の抑制機構についても新たな理解が示されました。この研究は、脳疾患の治療への道を開き、脳の複雑な構造と機能に対する深い理解を提供する可能性があります。
<関連情報>
- https://www.ibs.re.kr/cop/bbs/BBSMSTR_000000000738/selectBoardArticle.do
- https://www.nature.com/articles/s41583-023-00724-7
脳におけるGABAの緊張制御と認知機能 GABA tone regulation and its cognitive functions in the brain
Wuhyun Koh,Hankyul Kwak,Eunji Cheong & C. Justin Lee
Nature Reviews Neuroscience Published:26 July 2023
DOI:https://doi.org/10.1038/s41583-023-00724-7
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.
