Kim Yumi, Jang Jinyoung, Kim Hyun Jin, Park Myoung Kyu
Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea.
Korean J Physiol Pharmacol. 2018 Nov;22(6):721-729. doi: 10.4196/kjpp.2018.22.6.721. Epub 2018 Oct 25.
GABAergic control over dopamine (DA) neurons in the substantia nigra is crucial for determining firing rates and patterns. Although GABA activates both GABA and GABA receptors distributed throughout the somatodendritic tree, it is currently unclear how regional GABA receptors in the soma and dendritic compartments regulate spontaneous firing. Therefore, the objective of this study was to determine actions of regional GABA receptors on spontaneous firing in acutely dissociated DA neurons from the rat using patch-clamp and local GABA-uncaging techniques. Agonists and antagonists experiments showed that activation of either GABA receptors or GABA receptors in DA neurons is enough to completely abolish spontaneous firing. Local GABA-uncaging along the somatodendritic tree revealed that activation of regional GABA receptors limited within the soma, proximal, or distal dendritic region, can completely suppress spontaneous firing. However, activation of either GABA or GABA receptor equally suppressed spontaneous firing in the soma, whereas GABA receptor inhibited spontaneous firing more strongly than GABA receptor in the proximal and distal dendrites. These regional differences of GABA signals between the soma and dendritic compartments could contribute to our understanding of many diverse and complex actions of GABA in midbrain DA neurons.
黑质中γ-氨基丁酸(GABA)能对多巴胺(DA)神经元的控制对于确定放电频率和模式至关重要。尽管GABA能激活分布于整个胞体树突的GABA和GABA受体,但目前尚不清楚胞体和树突区域的GABA受体如何调节自发放电。因此,本研究的目的是利用膜片钳和局部GABA解笼技术,确定区域GABA受体对大鼠急性分离的DA神经元自发放电的作用。激动剂和拮抗剂实验表明,激活DA神经元中的GABA受体或GABA受体足以完全消除自发放电。沿胞体树突进行局部GABA解笼实验表明,局限于胞体、近端或远端树突区域的区域GABA受体的激活可完全抑制自发放电。然而,GABA或GABA受体的激活在胞体中同样抑制自发放电,而在近端和远端树突中,GABA受体比GABA受体更强烈地抑制自发放电。胞体和树突区域之间GABA信号的这些区域差异有助于我们理解GABA在中脑DA神经元中的多种复杂作用。