Emergence of Bursting Activity in Connected Neuronal Sub-Populations

Uniform and modular primary hippocampal cultures from embryonic rats were grown on commercially available micro-electrode arrays to investigate network activity with respect to development and integration of different neuronal populations. Modular networks consisting of two confined active and inter-connected sub-populations of neurons were realized by means of bi-compartmental polydimethylsiloxane structures. Spontaneous activity in both uniform and modular cultures was periodically monitored, from three up to eight weeks after plating. Compared to uniform cultures and despite lower cellular density, modular networks interestingly showed higher firing rates at earlier developmental stages, and network-wide firing and bursting statistics were less variable over time. Although globally less correlated than uniform cultures, modular networks exhibited also higher intra-cluster than inter-cluster correlations, thus demonstrating that segregation and integration of activity coexisted in this simple yet powerful in vitro model. Finally, the peculiar synchronized bursting activity shown by confined modular networks preferentially propagated within one of the two compartments (‘dominant’), even in cases of perfect balance of firing rate between the two sub-populations. This dominance was generally maintained during the entire monitored developmental frame, thus suggesting that the implementation of this hierarchy arose from early network development.