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Significance Tonic inhibition plays critical roles in cognitive functions under physiological and pathological conditions by controlling neuronal excitability. Although we have previously reported that cerebellar tonic inhibition is critically dependent on both the synthesis of GABA through monoamine oxidase B (MAOB) enzyme and the release via the bestrophin 1 (Best1) channel, the role of astrocytic GABA in cerebellar function in vivo has remained elusive. Here, we report that a reduction of tonic GABA release by genetic or pharmacological removal of Best1 or MAOB caused enhanced neuronal excitability, synaptic transmission, and motor performance on the rotarod test, whereas an augmentation of tonic GABA release by astrocyte-specific overexpression of MAOB caused opposite results. Our findings suggest the actions of astrocytic GABA in excitation/inhibition balance and motor coordination.

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