Spatial navigation through evolution: a single-cell atlas of the mammalian entorhinal cortex

Ralbovszki, D. M.; Westfall, J. J.; Mori, Y.; Tahas, S. A.; Bertelsen, M. F.; Korshunova, I.; Skov, J.; Gorodkin, J.; Hemberg, M.; Seemann, E. S.; Hall, V.; Witter, M.; Khodosevich, K.

doi:10.64898/2026.05.07.723541

bioRxiv · 10.64898/2026.05.07.723541

Spatial navigation through evolution: a single-cell atlas of the mammalian entorhinal cortex

Ralbovszki, D. M.·Westfall, J. J.·Mori, Y.·Tahas, S. A.·Bertelsen, M. F.·Korshunova, I.·Skov, J.·Gorodkin, J.·Hemberg, M.·Seemann, E. S.·Hall, V.·Witter, M.·Khodosevich, K.

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Abstract

Spatial navigation is a fundamental mammalian ability, supported by the entorhinal cortex (EC), a structurally conserved yet functionally diverse region across mammalian species. However, how molecular signaling underlies both shared and species-specific navigational strategies remains unclear. Here, we present a cross-species single-cell atlas of the EC from human, Hamadryas baboon, mouse, and Egyptian fruit bat - species spanning distinct evolutionary lineages and navigational demands, including true 3D navigation in bats. Using this resource, we identify conserved principal neuron populations as well as species-specific innovations, including mixed-layer or functional identities and fruit bat-specific subtypes. GABAergic interneurons neurons show strong conservation of somatostatin (SST) and parvalbumin (PV) families, while VIP GABAergic neurons exhibit pronounced species-specific divergence, with an expanded repertoire in primates. Integration with whole-brain diffusion tensor imaging reveals conserved and species-specific connectivity between the EC, hippocampus, and sensory cortices. Major species-specific cellular innovations were further validated using orthogonal histological approaches, confirming their anatomical and laminar organization. Overall, this atlas provides a comparative framework available for the research community to dissect the molecular, cellular, and circuit principles underlying conserved and specialized spatial navigation across mammals.

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Ralbovszki, D. M., Westfall, J. J., Mori, Y., Tahas, S. A., Bertelsen, M. F., Korshunova, I., Skov, J., Gorodkin, J., Hemberg, M., Seemann, E. S., Hall, V., Witter, M., Khodosevich, K.. 2026-05-07. Spatial navigation through evolution: a single-cell atlas of the mammalian entorhinal cortex. https://doi.org/10.64898/2026.05.07.723541

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