Emergence of Assortative Mixing between Clusters of Cultured Neurons

Abstract

The analysis of the activity of neuronal cultures is considered to be a good proxy of the functional connectivity of in vivo neuronal tissues. Thus, the functional complex network inferred from activity patterns is a promising way to unravel the interplay between structure and functionality of neuronal systems. Here, we monitor the spontaneous self-sustained dynamics in neuronal cultures formed by interconnected aggregates of neurons ( clusters). Dynamics is characterized by the fast activation of groups of clusters in sequences termed bursts. The analysis of the time delays between clusters' activations within the bursts allows the reconstruction of the directed functional connectivity of the network. We propose a method to statistically infer this connectivity and analyze the resulting properties of the associated complex networks. Surprisingly enough, in contrast to what has been reported for many biological networks, the clustered neuronal cultures present assortative mixing connectivity values, meaning that there is a preference for clusters to link to other clusters that share similar functional connectivity, as well as a rich-club core, which shapes a ‘connectivity backbone’ in the network. These results point out that the grouping of neurons and the assortative connectivity between clusters are intrinsic survival mechanisms of the culture.

Author Summary

The architecture of neuronal cultures is the result of an intricate self-organization process that balances structural and dynamical demands. We observe that when the motility of neurons is allowed, these neurons organize into compact clusters. These neuronal assemblies have an intrinsic synchronous activity that makes the whole cluster firing at unison. Clusters connect to their neighbors to form a network with rich spontaneous dynamics. This dynamics ultimately shapes a directed functional network whose properties are investigated using network descriptors. We find that the networks are formed such that preference in connectivity between clusters is based on the similarity between their activity, a property that is called assortative mixing in networks' language. This particular choice of connectivity correlations must be rooted to basic survival mechanisms for the neurons constituting the culture.