Report Spiny projection neurons exhibit transcriptional signatures within subregions of the dorsal striatum

The dorsal striatum is organized into functional territories defined by corticostriatal inputs onto both direct and indirect spiny projection neurons (SPNs), the major cell types within the striatum. In addition to circuit connectivity, striatal domains are likely defined by the spatially determined transcriptomes of SPNs them-selves. To identify cell-type-specific spatiomolecular signatures of direct and indirect SPNs within dorso-medial, dorsolateral, and ventrolateral dorsal striatum, we used RNA profiling in situ hybridization with probes to >98% of protein coding genes. We demonstrate that the molecular identity of SPNs is mediated by hundreds of differentially expressed genes across territories of the striatum, revealing extraordinary het-erogeneity in the expression of genes that mediate synaptic function in both direct and indirect SPNs. This deep insight into the complex spatiomolecular organization of the striatum provides a foundation for un-derstanding both normal striatal function and for dissecting region-specific dysfunction in disorders of the striatum.