Sharp cell-type-identity changes differentiate the retrosplenial cortex from the neocortex

The laminae of the neocortex are fundamental processing layers of the mammalian brain. Notably, such laminae are believed to be relatively stereotyped across short spatial scales such that shared laminae between nearby brain regions exhibit similar constituent cells. Here, we consider a potential exception to this rule by studying the retrosplenial cortex (RSC), a brain region known for sharp cytoarchitectonic differences across its granular-dysgranular border. Using a variety of transcriptomics techniques, we identify, spatially map, and interpret the excitatory cell-type landscape of the mouse RSC. In doing so, we uncover that RSC gene expression and cell types change sharply at the granular-dysgranular border. Additionally, supposedly homologous laminae between the RSC and the neocortex are effectively wholly distinct in their cell-type composition. In collection, the RSC exhibits a variety of intrinsic cell-type specializations and embodies an organizational principle wherein cell-type identities can vary sharply within and between brain regions. [Display omitted] •The RSC exhibits sharp changes in cell-type identity across subregions•Sharp changes in cellular identity are not resolvable across neocortical regions•Some RSC laminae exhibit distinct transcriptomic profiles relative to the neocortex•RSC laminar cell-type identities can vary sharply within and across brain regions Sullivan et al. identify sharp cell-type-identity changes across subregions of the mouse retrosplenial cortex (RSC) and further show that several RSC laminae have distinct transcriptomic profiles relative to corresponding neocortical layers. These findings illustrate that RSC cell-type organization is specialized relative to the neocortex.