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.

Highlights

  • The theory of complex networks [1,2,3,4,5] has proven to be a useful framework for the study of the interplay between structure and functionality in social, technological, and biological systems

  • Structural connectivity corresponds to the anatomical description of brain circuits whereas the functional connectivity is related to the statistical dependence between neuronal activity

  • Our work provides a prominent example of the existence of assortativity in biological networks, and illustrates the utility of clustered neuronal cultures to investigate topological traits and the emergence of complex phenomena, such as self-organization and resilience, in living neuronal networks

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Summary

Introduction

The theory of complex networks [1,2,3,4,5] has proven to be a useful framework for the study of the interplay between structure and functionality in social, technological, and biological systems. A complex network is no more than a specific representation of the interactions between the elements of the system in terms of nodes (elements) and links (interactions) in a graph. One of the major challenges in biology and neuroscience is the ultimate understanding of the structure and function of neuronal systems, in particular the human brain, whose representation in terms of complex networks is especially appealing [9,10]. In this case, structural connectivity corresponds to the anatomical description of brain circuits whereas the functional connectivity is related to the statistical dependence between neuronal activity

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