RT Journal Article T1 Human Purkinje cells outperform mouse Purkinje cells in dendritic complexity and computational capacity A1 Masoli, Stefano A1 Sanchez Ponce, Diana A1 Vrieler, Nora A1 Abu Haya, Karin A1 Lerner, Vitaly A1 Shahar, Tal A1 Nedelescu, Hermina A1 Rizza, Martina Francesca A1 Benavides Piccione, Ruth A1 DeFelipe, Javier A1 Yarom, Yosef A1 Muñoz Céspedes, Alberto A1 D’Angelo, Egidio AB Purkinje cells in the cerebellum are among the largest neurons in the brain and have been extensively investigated in rodents. However, their morphological and physiological properties remain poorly understood in humans. In this study, we utilized high-resolution morphological reconstructions and unique electrophysiological recordings of human Purkinje cells ex vivo to generate computational models and estimate computational capacity. An inter-species comparison showed that human Purkinje cell had similar fractal structures but were larger than those of mouse Purkinje cells. Consequently, given a similar spine density (2/μm), human Purkinje cell hosted approximately 7.5 times more dendritic spines than those of mice. Moreover, human Purkinje cells had a higher dendritic complexity than mouse Purkinje cells and usually emitted 2–3 main dendritic trunks instead of one. Intrinsic electro-responsiveness was similar between the two species, but model simulations revealed that the dendrites could process ~6.5 times (n = 51 vs. n = 8) more input patterns in human Purkinje cells than in mouse Purkinje cells. Thus, while human Purkinje cells maintained spike discharge properties similar to those of rodents during evolution, they developed more complex dendrites, enhancing computational capacity. PB Springer Nature YR 2024 FD 2024-01-02 LK https://hdl.handle.net/20.500.14352/119699 UL https://hdl.handle.net/20.500.14352/119699 LA eng NO Masoli, S., Sanchez-Ponce, D., Vrieler, N., Abu-Haya, K., Lerner, V., Shahar, T., Nedelescu, H., Rizza, M. F., Benavides-Piccione, R., DeFelipe, J., Yarom, Y., Munoz, A., & D’Angelo, E. (2024). Human Purkinje cells outperform mouse Purkinje cells in dendritic complexity and computational capacity. Communications Biology, 7(1). https://doi.org/10.1038/S42003-023-05689-Y NO We thank the NIH NeuroBioBank for providing post-mortem fixed human cerebellar cortex tissue samples; and we thank the Smith Family Foundation for their generous support towards providing and maintaining electrophysiological recording equipment at the Hebrew University. This research has received funding from the European Union’s Horizon 2020 Framework Program for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3) and Specific Grant Agreement No. 785907 (Human Brain Project SGA2). We acknowledge the use of Fenix Infrastructure resources, which are partially funded from the European Union’s Horizon 2020 research and innovation program through the ICEI project under the grant agreement No. 800858. Work supported by EBRAINS-Italy (IR00011) Project IR11– EBRAINS-Italy - M4C2 Line 3.1 of the PNRR, Action 3.1.1 – Funded by European Commission – NextGenerationEU (CUP B51E22000150006). We would like to thank Editage (www.editage.com) for English language editing. NO European Commission DS Docta Complutense RD 16 jun 2025