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 GABA_A-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.

γ-氨基丁酸 (GABA) 是 GABA 能突触释放的主要抑制性神经递质，介导快速作用的阶段性抑制。新出现的证据明确表明，大脑中存在少量的细胞外 GABA（GABA 音调），并诱导强直 GABA 电流，该电流以相对于阶段性抑制的缓慢时间尺度控制神经元活动。令人惊讶的是，研究表明合成 GABA 的神经胶质细胞（例如星形胶质细胞）通过非囊泡机制（例如通道介导的释放）释放 GABA，从而充当大脑中 GABA 音调的来源。在这篇综述中，我们首先概述了我们对调节不同大脑区域 GABA 张力的 GABA 合成、释放和清除的细胞特异性分子和细胞机制的理解方面的主要进展。_{接下来我们研究强直 GABA 电流通过突触外 GABA A}受体介导的机制调节突触传递和突触可塑性的多种方式。最后，我们讨论强直抑制在缓慢的时间尺度上调节认知功能的生理机制。在这篇综述中，我们强调紧张性 GABA 电流的认知功能超出了单纯的抑制作用，为未来研究 GABA 紧张性调节在正常和异常精神条件下的生理和病理生理作用奠定了基础。