Abstract

Hintiryan, Foster et al. present an online mouse cortico-striatal projectome describing projections from the entire cortex to dorsal striatum. Computational neuroanatomic analysis of these projections identified 29 distinct striatal domains. This connectomics approach was applied to characterize circuit-specific cortico-striatal connectopathies in a mouse model of Huntington disease and in monoamine oxidase (MAO) A/B knockout mice. Different cortical areas are organized into distinct intracortical subnetworks. The manner in which descending pathways from the entire cortex interact subcortically as a network remains unclear. We developed an open-access comprehensive mesoscale mouse cortico-striatal projectome: a detailed connectivity projection map from the entire cerebral cortex to the dorsal striatum or caudoputamen (CP) in rodents. On the basis of these projections, we used new computational neuroanatomical tools to identify 29 distinct functional striatal domains. Furthermore, we characterized different cortico-striatal networks and how they reconfigure across the rostral–caudal extent of the CP. The workflow was also applied to select cortico-striatal connections in two different mouse models of disconnection syndromes to demonstrate its utility for characterizing circuitry-specific connectopathies. Together, our results provide the structural basis for studying the functional diversity of the dorsal striatum and disruptions of cortico-basal ganglia networks across a broad range of disorders.