Vision-dependent specification of cell types and function in the developing cortex

The role of postnatal experience in sculpting cortical circuitry, while long appreciated, is poorly understood at the level of cell types. We explore this in the mouse primary visual cortex (V1) using single-nucleus RNA sequencing, visual deprivation, genetics, and functional imaging. We find that vision selectively drives the specification of glutamatergic cell types in upper layers (L) (L2/3/4), while deeper-layer glutamatergic, GABAergic, and non-neuronal cell types are established prior to eye opening. L2/3 cell types form an experience-dependent spatial continuum defined by the graded expression of ∼200 genes, including regulators of cell adhesion and synapse formation. One of these genes, Igsf9b, a vision-dependent gene encoding an inhibitory synaptic cell adhesion molecule, is required for the normal development of binocular responses in L2/3. In summary, vision preferentially regulates the development of upper-layer glutamatergic cell types through the regulation of cell-type-specific gene expression programs. [Display omitted] •Three glutamatergic L2/3 cell types are specified after eye opening•L2/3 cell types are spatially segregated by graded transcriptomic distinctions•Vision is required for the graded expression of L2/3 cell type markers•Binocular function in L2/3 requires Igsf9b, a graded vision-dependent gene Transcriptomic, genetic, and functional analyses of the developing mouse primary visual cortex (V1) reveal that early sensory experience selectively influences the development of layer 2/3 glutamatergic neurons by regulating spatial and temporal gene expression programs.