Evolution of the cellular landscape in mammalian striatum

Buyukkahraman, G.; Caglayan, E.; Hoerpel, S. G.; Zhang, Y.; van Tussenbroek, I. A.; Orozco, C. G.; Oh, E.; Hopkins, W. D.; Sherwood, C. C.; Roberts, T. F.; Vernes, S. C.; Konopka, G.

doi:10.1101/2025.04.20.649707

bioRxiv · 10.1101/2025.04.20.649707

Evolution of the cellular landscape in mammalian striatum

Buyukkahraman, G.·Caglayan, E.·Hoerpel, S. G.·Zhang, Y.·van Tussenbroek, I. A.·Orozco, C. G.·Oh, E.·Hopkins, W. D.·Sherwood, C. C.·Roberts, T. F.·Vernes, S. C.·Konopka, G.

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Abstract

The dorsal striatum is important for highly specialized functions including movement, learning, and habit formation. However, it is not known if species-specialized behaviors are associated with cellular specializations in the striatum. Here, we compared single-nucleus RNA sequencing (snRNA-seq) data from human, chimpanzee, rhesus macaque, common marmoset, and pale spear-nosed bat caudate (CN) and putamen (Pu) separately as well as mouse caudoputamen (C-Pu), which represents divergence among species spanning approximately 94 million years of evolution. We observed a lower neuron-to-glia ratio in primate striata compared to non-primates, reflecting the allometric scaling of neuron density and relative glia density invariance in larger brains. Among neurons, eccentric spiny projection neurons (eSPNs) - an SPN of unknown function - showed significantly lower proportions in non-primate striata for both CN and Pu. Focusing on the heterogeneity within interneurons, we identified two bat striatal interneuron cell types that are nearly absent in other species: which express LMO3, and co-express FOXP2 and TSHZ2. Other striatal interneurons also showed significantly differential abundance between primates and non-primates. In summary, we provide a comprehensive snRNA- seq dataset of dorsal striatum, identify novel interneuron innovations in bat, and uncover fundamental cellular composition differences between primate and non-primate striata.

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Buyukkahraman, G., Caglayan, E., Hoerpel, S. G., Zhang, Y., van Tussenbroek, I. A., Orozco, C. G., Oh, E., Hopkins, W. D., Sherwood, C. C., Roberts, T. F., Vernes, S. C., Konopka, G.. 2025-04-21. Evolution of the cellular landscape in mammalian striatum. https://doi.org/10.1101/2025.04.20.649707

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