Mammalian brains vary in size, structure and function, but the extent to which evolutionarily novel cell types contribute to this variation remains unresolved1–4. Previous studies suggest that there is a primate-specific population of striatal inhibitory interneurons—the TAC3 interneurons5. However, broader taxonomic and developmental characterization is required to address novelty in cell-type evolution. Here we examine gene expression in inhibitory neurons across 10 mammalian species, spanning 160 million years of divergence from primates. We find that the initial class of newborn TAC3 interneurons specified during development represents an ancestral, medial ganglionic eminence (MGE)-derived striatal population that is also present in pig and ferret cortex. This discovery prompted a re-examination of Glires, including mice, which are thought to lack the TAC3 type5,6. Targeted enrichment of MGE precursors in mice revealed conservation of the TAC3 initial class, camouflaged by reduced expression of Tac2 (the mouse orthologue of TAC3) and a gain of Th expression. Extending our analysis to the adult striatum further supported the homology of primate TAC3 and mouse Th striatal interneurons, and also uncovered a rare Tac2 subpopulation in the mouse ventromedial striatum. This study suggests that initial classes of telencephalic inhibitory neurons are largely conserved, and that during evolution, neuronal types in the mammalian brain change through redistribution and fate refinement, rather than by derivation of novel precursors early in development.
