Continuous and Discrete Neuron Types of the Adult Murine Striatum

The mammalian striatum is involved in many complex behaviors and yet is composed largely of a single neuron class: the spiny projection neuron (SPN). It is unclear to what extent the functional specialization of the striatum is due to the molecular specialization of SPN subtypes. We sought to define the molecular and anatomical diversity of adult SPNs using single-cell RNA sequencing (scRNA-seq) and quantitative RNA in situ hybridization (ISH). We computationally distinguished discrete versus continuous heterogeneity in scRNA-seq data and found that SPNs in the striatum can be classified into four major discrete types with no implied spatial relationship between them. Within these discrete types, we find continuous heterogeneity encoding spatial gradients of gene expression and defining anatomical location in a combinatorial mechanism. Our results suggest that neuronal circuitry has a substructure at far higher resolution than is typically interrogated, which is defined by the precise identity and location of a neuron.