Self-organization of in vitro neuronal assemblies drives to complex network topology.

Activity-dependent self-organization plays an important role in the formation of specific and stereotyped connectivity patterns in neural circuits. By combining neuronal cultures, and tools with approaches from network neuroscience and information theory, we can study how complex network topology emerges from local neuronal interactions. We constructed effective connectivity networks using a transfer entropy analysis of spike trains recorded from rat embryo dissociated hippocampal neuron cultures between 6 and 35 days in vitro to investigate how the topology evolves during maturation. The methodology for constructing the networks considered the synapse delay and addressed the influence of firing rate and population bursts as well as spurious effects on the inference of connections. We found that the number of links in the networks grew over the course of development, shifting from a segregated to a more integrated architecture. As part of this progression, three significant aspects of complex network topology emerged. In agreement with previous in silico and in vitro studies, a small-world architecture was detected, largely due to strong clustering among neurons. Additionally, the networks developed in a modular topology, with most modules comprising nearby neurons. Finally, highly active neurons acquired topological characteristics that made them important nodes to the network and integrators of modules. These findings leverage new insights into how neuronal effective network topology relates to neuronal assembly self-organization mechanisms.