Interneuron diversity in the human dorsal striatum

Abstract Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangle the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their transcriptional structure in the human dorsal striatum. We propose a new taxonomy of striatal interneurons with eight main classes and fourteen subclasses and provide their specific markers and some quantitative FISH validation, particularly for a novel PTHLH-expressing population. For the most abundant populations, PTHLH and TAC3, we found matching known mouse interneuron populations based on key functional genes such as ion channels and synaptic receptors. Remarkably, human TAC3 and mouse Th populations share important similarities including the expression of the neuropeptide tachykinin 3. Finally, we were able to integrate other published datasets supporting the generalizability of this new harmonized taxonomy.