Intrinsic electrophysiological properties predict variability in morphology and connectivity among striatal...

Determining the cellular content of the nervous system in terms of cell types and the rules of their connectivity represents a fundamental challenge to the neurosciences. The recent advent of high-throughput techniques, such as single-cell RNA-sequencing has allowed for greater resolution in the identification of cell types and/or states. Although most of the current neuronal classification schemes comprise discrete clusters, several recent studies have suggested that, perhaps especially, within the striatum, neuronal populations exist in continua, with regards to both their molecular and electrophysiological properties. Whether these continua are stable properties, established during development, or if they reflect acute differences in activity-dependent regulation of critical genes is currently unknown. We set out to determine whether gradient-like molecular differences in the recently described Pthlh-expressing inhibitory interneuron population, which contains the Pvalb-expressing cells, correlate with differences in morphological and connectivity properties. We show that morphology and long-range inputs correlate with a spatially organized molecular and electrophysiological gradient of Pthlh-interneurons, suggesting that the processing of different types of information (by distinct anatomical striatal regions) has different computational requirements.