Cholinergic deficits selectively boost cortical intratelencephalic control of striatum in male Huntington's disease model mice.

ABSTRACT: Huntington's disease (HD) is a progressive, neurodegenerative disease caused by a CAG triplet expansion in huntingtin. Although corticostriatal dysfunction has long been implicated in HD, the determinants and pathway specificity of this pathophysiology are not fully understood. Here, using a male zQ175^+/- knock-in mouse model of HD we carry out optogenetic interrogation of intratelencephalic and pyramidal tract synapses with principal striatal spiny projection neurons (SPNs). These studies reveal that the connectivity of intratelencephalic, but not pyramidal tract, neurons with direct and indirect pathway SPNs increased in early symptomatic zQ175^+/- HD mice. This enhancement was attributable to reduced pre-synaptic inhibitory control of intratelencephalic terminals by

SUBMITTER: Pancani T 

PROVIDER: S-EPMC10011605 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature