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Functional Dissection of Basal Ganglia Inhibitory Inputs onto Substantia Nigra Dopaminergic Neurons.
Cell Reports ( IF 8.8 ) Pub Date : 2020-09-15 , DOI: 10.1016/j.celrep.2020.108156
Rebekah C Evans 1 , Emily L Twedell 1 , Manhua Zhu 1 , Jefferson Ascencio 1 , Renshu Zhang 1 , Zayd M Khaliq 1
Affiliation  

Substantia nigra (SNc) dopaminergic neurons respond to aversive stimuli with inhibitory pauses in firing followed by transient rebound activation. We tested integration of inhibitory synaptic inputs onto SNc neurons from genetically defined populations in dorsal striatum (striosome and matrix) and external globus pallidus (GPe; parvalbumin- and Lhx6-positive), and examined their contribution to pause-rebound firing. Activation of striosome projections, which target “dendron bouquets” in the pars reticulata (SNr), consistently quiets firing and relief from striosome inhibition triggers rebound activity. Striosomal inhibitory postsynaptic currents (IPSCs) display a prominent GABA-B receptor-mediated component that strengthens the impact of SNr dendrite synapses on somatic excitability and enables rebounding. By contrast, GPe projections activate GABA-A receptors on the soma and proximal dendrites but do not result in rebounding. Lastly, optical mapping shows that dorsal striatum selectively inhibits the ventral population of SNc neurons, which are intrinsically capable of rebounding. Therefore, we define a distinct striatonigral circuit for generating dopamine rebound.



中文翻译:

基底神经节抑制输入到黑质多巴胺能神经元的功能解剖。

黑质 (SNc) 多巴胺能神经元对厌恶刺激做出反应,在放电时会出现抑制性暂停,随后会出现短暂的反弹激活。我们测试了抑制性突触输入整合到来自背侧纹状体(纹状体和基质)和外部苍白球(GPe;小白蛋白和 Lhx6 阳性)中基因定义群体的 SNc 神经元,并检查了它们对暂停反弹放电的贡献。以网状部 (SNr) 中的“树突花束”为目标的纹状体投射的激活,持续平息放电,纹状体抑制的缓解触发反弹活动。纹状体抑制性突触后电流 (IPSC) 显示出显着的 GABA-B 受体介导成分,可增强 SNr 树突突触对躯体兴奋性的影响并实现反弹。相比之下,GPe 投射激活体细胞和近端树突上的 GABA-A 受体,但不会导致反弹。最后,光学映射显示背侧纹状体选择性地抑制腹侧 SNc 神经元群,这些神经元本质上具有反弹能力。因此,我们定义了一个独特的纹状体黑质回路来产生多巴胺反弹。

更新日期:2020-09-15
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