Brain-on-a-chip models to investigate the role of modularity, heterogeneity, and three-dimensionality on in vitro neuronal networks

The human brain is the most complex organ of our body. in which neurons are the interacting elements. These cells are coupled through physical connections and complex biochemical processes. They are able to self-organization and exhibit a rich repertoire of spatiotemporal patterns and dynamics states. However, because of such high complexity, understanding human physiology as well as pathogenesis is not straightforward. Set-ups for in vivo studies are often very complicated, time consuming, and with low reproducibility. For this reason, there is the need to develop new in vitro systems capable of mimicking as much as possible the human brain. In addition, a successful model would minimize animal use for drug screening applications, deliver a highly reproducible system, and significantly lower costs in light of the current demand for pharmacological development. Primary dissociated neuronal cultures are an elegant yet powerful experimental tool to investigate and describe both electrophysiological and morphological properties of neuronal networks, which guarantee a good trade-off between controllability/observability and similarity to the in vivo nervous system. The electrophysiological activity of such neuronal assemblies can be extracellularly recorded by means of Micro-Electrode Arrays (MEAs). Up to now, most of the works make use of homogeneous networks, which do not fully mimic the complex organization as well as the functional and structural complexity of the human brain in vivo. The goal of this research project is to recreate in vitro 2D and 3D engineered neuronal networks made up of interacting sub-populations to recreate interconnected brain regions on a chip.