PDF(Pubmed)
Abstract：
Functional deficits in basal ganglia (BG) circuits contribute to cognitive and motor dysfunctions in alcohol use disorder. Chronic alcohol exposure alters synaptic function and neuronal excitability in the dorsal striatum, but it remains unclear how it affects BG output that is mediated by the substantia nigra pars reticulata (SNr). Here, we describe a neuronal subpopulation-specific synaptic organization of striatal and subthalamic (STN) inputs to the medial and lateral SNr. Chronic alcohol exposure (CIE) potentiated dorsolateral striatum (DLS) inputs but did not change dorsomedial striatum and STN inputs to the SNr. Chemogenetic inhibition of DLS direct pathway neurons revealed an enhanced role for DLS direct pathway neurons in execution of an instrumental lever-pressing task. Overall, we reveal a subregion-specific organization of striatal and subthalamic inputs onto the medial and lateral SNr and find that potentiated DLS-SNr inputs are accompanied by altered BG control of action execution following CIE.
摘要：
基底神经节（BG）回路的功能缺陷导致酒精使用障碍的认知和运动功能障碍。慢性酒精暴露会改变背侧纹状体的突触功能和神经元兴奋性，但目前尚不清楚它如何影响由黑质网状结构(SNr)介导的BG输出。这里,我们描述了纹状体和丘脑下（STN）输入到内侧和外侧SNr的神经元亚群特异性突触组织。慢性酒精暴露（CIE）增强了背外侧纹状体（DLS）输入，但没有改变SNr的背内侧纹状体和STN输入。DLS直接途径神经元的化学遗传学抑制揭示了DLS直接途径神经元在执行工具杠杆按压任务中的作用增强。总的来说,我们揭示了纹状体和丘脑下输入到内侧和外侧SNr上的子区域特定组织，并发现增强的DLS-SNr输入伴随着对CIE后行为执行的BG控制的改变。
