Axonal Modulation of Striatal Dopamine Release by Local γ-Aminobutyric Acid (GABA) Signalling

被引:18
作者
Roberts, Bradley M. [1 ]
Lopes, Emanuel F. [1 ]
Cragg, Stephanie J. [1 ]
机构
[1] Univ Oxford, Ctr Integrat Neurosci, Dept Physiol Anat & Genet, Oxford OX1 3PT, England
关键词
dopamine; GABA; GABA(A) receptors; GABA(B) receptors; GABA transporters; Parkinson’ s disease; striatum; tonic inhibition;
D O I
10.3390/cells10030709
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 gamma-aminobutyric acid (GABA) acting via GABA(A) and GABA(B) receptors. We review evidence supporting the localisation of GABA(A) and GABA(B) 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(A) and GABA(B) 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.
引用
收藏
页数:17
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