Network size affects the complexity of activity in human iPSC-derived neuronal populations

Multi-electrode recording of neural activity in cultures offer opportunities for understanding how the structure of a network gives rise to function. Although it is hypothesized that network size is critical for determining the dynamics of activity, this relationship in human neural cultures remains largely unexplored. By applying new methods for analyzing neural activity to human iPSC derived cultures at either low-densities or high-densities, we uncovered the significant impacts that neuron number has on the individual neurophysiological properties of cells (such as firing rates), the collective behavior of the networks these cultures formed (as measured by entropy), and the relationship between the two. As a result, simply changing the densities of neurons generated dynamics and network behavior that differed not just in degree, but in kind. Beyond revealing the relationship between network structure and function, our findings provide a novel analytical framework to study diseases where network level activity is affected.