Exploring the Contribution of Thalamic and Hippocampal Input on Cortical Dynamics in a Brain-on-a-Chip Model

The huge connectivity of the brain and the cellular diversity, which characterize the neuronal populations in the different anatomical districts, are considered two of the main sources originating the complex patterns of electrophysiological activity. Despite the advancements in neurotechnologies, which allowed investigating the brain complexity with a high level of precision, the use of simplified in vitro brain-on-a-chip models results to be a widespread alternative. In the present work, we used an in vitro brain-regions-on-a-chip model to explore the role of thalamic and hippocampal neurons in modulating the dynamics of cortical ensembles. We recorded the emerging electrophysiological activity by means of Micro-Electrode Arrays (MEAs) paired with ad hoc polymeric structures in order to recreate interconnected heterogeneous networks. We demonstrated that two specific neuronal inputs (thalamic and hippocampal) modulated cortical dynamics differently. The observed variation in the cortical activity was sustained by a specific reorganization of the functional inhibitory connections with respect to the cortical homogeneous controls. In perspective, the possibility to design in vitro specific interconnected brain-regions-on-a-chip and to record their electrophysiological activity could be an alternative approach to investigate neurodegenerative pathologies affecting the connectivity among different neuronal populations.