A comprehensive excitatory input map of the striatum reveals novel functional organization.

The striatum integrates excitatory inputs from the cortex and the thalamus to control diverse functions. Although the striatum is thought to consist of sensorimotor, associative and limbic domains, their precise demarcations and whether additional functional subdivisions exist remain unclear. How striatal inputs are differentially segregated into each domain is also poorly understood. This study presents a comprehensive map of the excitatory inputs to the mouse striatum. The input patterns reveal boundaries between the known striatal domains. The most posterior striatum likely represents the 4th functional subdivision, and the dorsomedial striatum integrates highly heterogeneous, multimodal inputs. The complete thalamo-cortico-striatal loop is also presented, which reveals that the thalamic subregions innervated by the basal ganglia preferentially interconnect with motor-related cortical areas. Optogenetic experiments show the subregion-specific heterogeneity in the synaptic properties of striatal inputs from both the cortex and the thalamus. This projectome will guide functional studies investigating diverse striatal functions.

A comprehensive thalamocortical projection map at the mesoscopic level.

The thalamus relays sensori-motor information to the cortex and is an integral part of cortical executive functions. The precise distribution of thalamic projections to the cortex is poorly characterized, particularly in mouse. We employed a systematic, high-throughput viral approach to visualize thalamocortical axons with high sensitivity. We then developed algorithms to directly compare injection and projection information across animals. By tiling the mouse thalamus with 254 overlapping injections, we constructed a comprehensive map of thalamocortical projections. We determined the projection origins of specific cortical subregions and verified that the characterized projections formed functional synapses using optogenetic approaches. As an important application, we determined the optimal stereotaxic coordinates for targeting specific cortical subregions and expanded these analyses to localize cortical layer-preferential projections. This data set will serve as a foundation for functional investigations of thalamocortical circuits. Our approach and algorithms also provide an example for analyzing the projection patterns of other brain regions.