A Spatiomolecular Map of the Striatum

Abstract

Summary: The striatum is organized into two major outputs formed by striatal projection neuron (SPN) subtypes with distinct molecular identities. In addition, histochemical division into patch and matrix compartments represents an additional spatial organization, proposed to mirror a motor-motivation regionalization. To map the molecular diversity of patch versus matrix SPNs, we genetically labeled mu opioid receptor (Oprm1) expressing neurons and performed single-nucleus RNA sequencing. This allowed us to establish molecular definitions of patch, matrix, and exopatch SPNs, as well as identification of Col11a1+ striatonigral SPNs. At the tissue level, mapping the expression of candidate markers reveals organization of spatial domains, which are conserved in the non-human primate brain. The spatial markers are cell-type independent and instead represent a spatial code found across all SPNs within a spatial domain. The spatiomolecular map establishes a formal system for targeting and studying striatal subregions and SPNs subtypes, beyond the classical striatonigral and striatopallidal division. : Märtin et al. define the molecular identity of striatal projections neurons, focusing on the characterization of the patch and matrix compartments. Genetic labeling of mu opioid receptor (Oprm1)-expressing neurons reveals the identity of neuron subtypes, and also establishes spatial markers for the identification of subregions in striatum. Keywords: neuroanatomy, single-cell RNA-seq, basal ganglia, striatum, patch, matrix, striosome, oprm1, opioid, dopamine