Conservation and alteration of mammalian striatal interneurons

Mammalian brains vary in size, structure, and function, but the extent to which evolutionarily novel cell types contribute to this variation remains unresolved. Recent studies suggest there is a primate-specific population of striatal inhibitory interneurons, the TAC3 interneurons. However, broader taxonomic and developmental characterization is required to address novelty in cell type evolution. Here, we examine gene expression in inhibitory neurons across 11 mammalian species, spanning 160 million years divergence from primates. We find that the initial class of newborn TAC3 interneurons specified during development represents an ancestral, MGE-derived striatal population also present in pig and ferret cortex. This discovery prompted a reexamination of the Glire clade, including mice which are thought to lack the TAC3 type. Targeted enrichment of MGE precursors in mice reveals conservation of the TAC3 initial class, camouflaged by reduced expression of Tac2 (the mouse ortholog of TAC3) and a gain of Th expression. Extending our analysis to the adult striatum further supports the homology of primate TAC3 and mouse Th striatal interneurons, while uncovering a rare Tac2 subpopulation in 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. Overall design: 10x Genomics Chromium next GEM single cell 3' RNA-sequencing of developing ferret, pig, rat, rabbit, mouse, opossum and sugar glider developing brain.