Whole-brain input organization of Kremen1-positive striatal spiny projection neurons revealed by monosynaptic rabies tracing.

Determining the organization of inputs to subtypes of striatal spiny projection neurons (SPNs) is essential to understand how the striatum integrates information to regulate motor control and decision making. Here, we employed monosynaptic rabies tracing in Kremen1 2A-Cre knock-in mice to map inputs to Kremen1-positive (Kremen1 +) SPNs, a subtype enriched in patch (striosome) compartments of the dorsal striatum. Starter cells were broadly distributed along the rostrocaudal axis of the dorsal striatum. Whole-brain analysis revealed that Kremen1 + SPNs receive prominent inputs from motor, somatosensory, and prefrontal cortices, as well as from multiple thalamic nuclei. Additional inputs originated from the amygdala, basal ganglia, and midbrain regions, including dopaminergic populations. Quantitative analysis indicated a strong bias toward sensorimotor-related circuits. Together, these results provide a comprehensive whole-brain input map of Kremen1 + SPNs and suggest that these neurons are positioned to integrate cortical, thalamic, and neuromodulatory signals within basal ganglia networks to regulate motor function.