Department of Physiology, Anatomy and Genetics, Centre for Integrative Neuroscience and Oxford Parkinson's Disease Centre, University of Oxford, Oxford OX1 3PT, UK.
Cells. 2021 Mar 23;10(3):709. doi: 10.3390/cells10030709.
Striatal dopamine (DA) release is critical for motivated actions and reinforcement learning, and is locally influenced at the level of DA axons by other striatal neurotransmitters. Here, we review a wealth of historical and more recently refined evidence indicating that DA output is inhibited by striatal γ-aminobutyric acid (GABA) acting via GABA and GABA receptors. We review evidence supporting the localisation of GABA and GABA receptors to DA axons, as well as the identity of the striatal sources of GABA that likely contribute to GABAergic modulation of DA release. We discuss emerging data outlining the mechanisms through which GABA and GABA receptors inhibit the amplitude as well as modulate the short-term plasticity of DA release. Furthermore, we highlight recent data showing that DA release is governed by plasma membrane GABA uptake transporters on striatal astrocytes, which determine ambient striatal GABA tone and, by extension, the tonic inhibition of DA release. Finally, we discuss how the regulation of striatal GABA-DA interactions represents an axis for dysfunction in psychomotor disorders associated with dysregulated DA signalling, including Parkinson's disease, and could be a novel therapeutic target for drugs to modify striatal DA output.
纹状体多巴胺（DA）的释放对动机行为和强化学习至关重要，并且在 DA 轴突水平上受到其他纹状体神经递质的局部影响。在这里，我们回顾了大量历史和最近更精细的证据，表明纹状体γ-氨基丁酸（GABA）通过 GABA 和 GABA 受体作用抑制 DA 输出。我们回顾了支持 GABA 和 GABA 受体定位于 DA 轴突的证据，以及可能有助于 GABA 能调制 DA 释放的纹状体 GABA 来源的身份。我们讨论了概述 GABA 和 GABA 受体通过何种机制抑制 DA 释放幅度以及调节其短期可塑性的新兴数据。此外，我们强调了最近的数据表明，DA 释放受纹状体星形胶质细胞上的质膜 GABA 摄取转运蛋白调节，该蛋白决定了纹状体内的 GABA 紧张度，并因此调节 DA 释放的紧张性抑制。最后，我们讨论了纹状体 GABA-DA 相互作用的调节如何代表与 DA 信号转导失调相关的运动障碍的功能障碍轴，包括帕金森病，并且可能成为改变纹状体 DA 输出的药物的新的治疗靶点。
