Structural Modularity Tunes Mesoscale Criticality in Biological Neuronal Networks

Numerous studies suggest that biological neuronal networks self-organize toward a critical state with stable recruitment dy-namics. Individual neurons would then statistically activate exactly one further neuron during activity cascades termed neuro-nal avalanches. Yet, it is unclear if and how this can be reconciled with the explosive recruitment dynamics within neocortical minicolumns in vivo and within neuronal clusters in vitro, which indicates that neurons form supercritical local circuits. Theoretical studies propose that modular networks with a mix of regionally subcritical and supercritical dynamics would create apparently critical dynamics, resolving this inconsistency. Here, we provide experimental support by manipulat-ing the structural self-organization process of networks of cultured rat cortical neurons (either sex). Consistent with the pre-diction, we show that increasing clustering in neuronal networks developing in vitro strongly correlates with avalanche size distributions transitioning from supercritical to subcritical activity dynamics. Avalanche size distributions approximated a power law in moderately clustered networks, indicating overall critical recruitment. We propose that activity-dependent self -organization can tune inherently supercritical networks toward mesoscale criticality by creating a modular structure in neuro-nal networks.