Control of motor coordination by astrocytic tonic GABA release through modulation of excitation/inhibition balance in cerebellum

Title
Control of motor coordination by astrocytic tonic GABA release through modulation of excitation/inhibition balance in cerebellum
Authors
이창준우준성김정연안희영권재김선필Joo Ok MinDae-Si KangYoo Sung KimGuk Hwa JungHyun Jung ParkInsop ShimHyung-Gun KimBo-Eun Yoon
Issue Date
2018-05
Publisher
Proceedings of the National Academy of Sciences of the United States of America
Citation
VOL 115, NO 19-5009
Abstract
Tonic inhibition in the brain is mediated through an activation of extrasynaptic GABAA receptors by the tonically released GABA, resulting in a persistent GABAergic inhibitory action. It is one of the key regulators for neuronal excitability, exerting a powerful action on excitation/inhibition balance. We have previously reported that astrocytic GABA, synthesized by monoamine oxidase B (MAOB), mediates tonic inhibition via GABA-permeable bestrophin 1 (Best1) channel in the cerebellum. However, the role of astrocytic GABA in regulating neuronal excitability, synaptic transmission, and cerebellar brain function has remained elusive. Here, we report that a reduction of tonic GABA release by genetic removal or pharmacological inhibition of Best1 or MAOB caused an enhanced neuronal excitability in cerebellar granule cells (GCs), synaptic transmission at the parallel fiber-Purkinje cell (PF-PC) synapses, and motor performance on the rotarod test, whereas an augmentation of tonic GABA release by astrocyte-specific overexpression of MAOB resulted in a reduced neuronal excitability, synaptic transmission, and motor performance. The bidirectional modulation of astrocytic GABA by genetic alteration of Best1 or MAOB was confirmed by immunostaining and in vivo microdialysis. These findings indicate that astrocytes are the key player in motor coordination through tonic GABA release by modulating neuronal excitability and could be a good therapeutic target for various movement and psychiatric disorders, which show a disturbed excitation/inhibition balance.
URI
http://pubs.kist.re.kr/handle/201004/69748
ISSN
0027-8424
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KIST Publication > Article
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