Phenotypic variation of transcriptomic cell types in mouse motor cortex

Single-cell transcriptomic, morphological and electrophysiological characteristics are combined to classify more than 1,300 neurons from mouse motor cortex. Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties(1,2). Most existing neural taxonomies are based on either transcriptomic(3,4) or morpho-electric(5,6) criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells(7). Here we used Patch-seq(8) to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of more than 1,300 neurons in adult mouse primary motor cortex, providing a morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (those expressing Vip, Pvalb, Sst and so on) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neuronal types in the neocortex do not always form discrete entities. Instead, neurons form a hierarchy that consists of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families.

Automated summary

The study combines single-cell transcriptomic, morphological, and electrophysiological characteristics to classify over 1,300 neurons from the mouse motor cortex, revealing extreme diversity in gene expression, morphology, and electrophysiology. While broad families of transcriptomic types exhibit distinct morpho-electric phenotypes, individual transcriptomic types within the same family show a continuum of variability in morphology and electrophysiology without clear boundaries between them, indicating that neuronal types in the neocortex do not always form discrete entities.