Cell Density Impacts Population Activity in Human iPSC-Derived Neural Networks.

Overview

1. Department of Physics and Astronomy, University of Rochester, Rochester, New York 14642
2. Del Monte Institute for Neuroscience, University of Rochester School of Medicine, Rochester, New York 14642
3. Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Signaling Mechanisms in Neurological Disorders, Paris 75014, France
4. Institut des Sciences Biologiques, CNRS, Paris 75005, France
5. Department of Anthropology, University of California, San Diego, La Jolla, California 92093
6. Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642
7. Center for Visual Science, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642
8. Intellectual Development and Disability Research Center, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642
9. Department of Biomedical Engineering, Hajim School of Engineering, University of Rochester, Rochester, New York 14642

Abstract

Multi-electrode recording of neuronal activity in cultures offer opportunities for understanding how the structure of a network gives rise to function. Neuronal cultures derived from human induced pluripotent stem cells (iPSCs) from male and female individuals are often plated at highly variable cell densities across studies, but its impact on neuronal activity remains poorly understood. We found that properties such as the mean firing rate of the individual cells, the pairwise correlations between cells, and the entropy of the population all changed significantly with changes in culture density. We used a maximum entropy model to capture the structure of the population activity using only the firing rates and correlations, and we found that the model performed best at the highest densities, suggesting that changes in activity reflected differences in structure of interactions between neurons across scales of complexity. Our work thus shows that culture density is an important experimental parameter that impacts neuronal activity in human iPSC-derived cultures. Additionally, our findings provide an analytical framework to study population activity in neuronal cultures including those from patient populations where a disease process may impact network activity.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Code accessibility

The analysis was performed with MATLAB 2022b on Windows operating system. The code described in the paper is freely available online at https://github.com/krishnanURMC/Uzun_eNeuro_2026. The code is available as Extended Data (https://doi.org/10.1523/ENEURO.0176-24.2026.d1).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 4 keywords, 10 MeSH terms, 6 funders, 67 references, 2 RRIDs.

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This paper

Uzun, Y. S., Santos, R., Marchetto, M. C., & Padmanabhan, K. (2026). Cell Density Impacts Population Activity in Human iPSC-Derived Neural Networks. eNeuro, 13(5), ENEURO.0176-24.2026. https://doi.org/10.1523/eneuro.0176-24.2026

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