Early Alterations of Motor Learning and Corticostriatal Network Activity in a Huntington's Disease Mouse Model.

Huntington's disease (HD) is a neurodegenerative disorder that presents motor, cognitive, and psychiatric symptoms as it progresses. Prior to motor symptoms onset, alterations, and dysfunctions in the corticostriatal projections have been described along with cognitive deficits, but the sequence of early alterations of brain circuits is largely unknown. There is thus a crucial need to identify early alterations that precede symptoms and that could be used as potential early disease markers.

Spatiotemporal reorganization of corticostriatal networks encodes motor skill learning.

Motor skill learning requires the activity of the dorsal striatum, with a differential global implication of the dorsomedial and dorsolateral territories. We investigate here whether and how specific striatal neurons encode the acquisition and consolidation of a motor skill. Using ex vivo two-photon calcium imaging after rotarod training, we report that highly active (HA) striatal populations arise from distinct spatiotemporal reorganization in the dorsomedial (DMS) and dorsolateral (DLS) striatum networks and are correlated with learning performance.