Cholinergic deficits selectively boost cortical intratelencephalic control of the striatum in Huntington’s disease
semanticscholar(2021)
摘要
Huntington’s disease (HD) is a progressive, neurodegenerative disease caused by a CAG triplet expansion in the huntingtin gene. Although corticostriatal dysfunction has long been implicated in HD, the determinants and pathway specificity of this pathophysiology remain a matter of speculation. To help fill this gap, the zQ175+/- knockin mouse model of HD was studied using approaches that allowed optogenetic interrogation of intratelencephalic (IT) and pyramidal tract (PT) connections with principal striatal spiny projection neurons (SPNs). These studies revealed that the connectivity of IT, but not PT, neurons with direct and indirect pathway SPNs increased in early symptomatic zQ175+/- HD mice. This enhancement was attributable to reduced inhibitory control of IT terminals by striatal cholinergic interneurons (ChIs). Lowering mutant huntingtin selectively in ChIs with a virally-delivered zinc finger repressor protein normalized striatal acetylcholine release and IT functional connectivity – revealing a novel node in the network underlying corticostriatal pathophysiology in HD.
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要