Functional Inhibitory Connections Modulate the Electrophysiological Activity Patterns of Cortical-Hippocampal Ensembles

The brain is a complex organ composed of billions of neurons connected through excitatory and inhibitory synapses. Its structure reveals a modular topological organization, where neurons are arranged in interconnected assemblies. The generated patterns of electrophysiological activity are shaped by two main factors: network heterogeneity and the topological properties of the underlying connectivity that strongly push the dynamics toward different brain-states. In this work, we exploited an innovative polymeric structure coupled to Micro-Electrode Arrays (MEAs) to recreate in vitro heterogeneous interconnected (modular) neuronal networks made up of cortical and hippocampal neurons. We investigated the propagation of spike sequences between the two interconnected subpopulations during the networks' development, correlating functional and structural connectivity to dynamics. The simultaneous presence of two neuronal types shaped the features of the functional connections (excitation vs. inhibition), orchestrating the emerging patterns of electrophysiological activity. In particular, we found that hippocampal neurons mostly project inhibitory connections toward the cortical counterpart modulating the temporal scale of the population events (network bursts). In contrast, cortical neurons establish a larger amount of intrapopulation connections. Moreover, we proved topological properties such as small-worldness, degree distribution, and modularity of neuronal assemblies were favored by the physical environment where networks developed and matured.