Vision sculpts a continuum of L2/3 cell types in the visual cortex during the critical period

Abstract

SummaryWe previously reported that vision specifies Layer 2/3 (L2/3) glutamatergic cell-type identity in the primary visual cortex (V1). Using unsupervised clustering of single-nucleus RNA-sequencing data, we identified molecularly distinct L2/3 cell types in normal-reared (NR) and dark-reared (DR) mice, but the two sets exhibited poor correspondence. Here, we show that classification of cell types was confounded in DR by vision-dependent gene programs that are orthogonal to gene programs underlying cell-type identity. A focused clustering analysis successfully matches cell types between DR and NR, suggesting that cell identity-defining gene programs persist under vision deprivation but are overshadowed by vision-dependent transcriptomic variation. Using multi-tasking theory we show that L2/3 cell types form a continuum between three cell-archetypes. Visual deprivation markedly shifts this distribution along the continuum. Thus, dark-rearing markedly influences cell states thereby masking cell-type-identities and changes the distribution of L2/3 types along a transcriptomic continuum.