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

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.