Modularity and neuronal heterogeneity: Two properties that influence in vitro neuropharmacological experiments.

Introduction: The goal of this work is to prove the relevance of the experimental model ( in vitro neuronal networks in this study) when drug-delivery testing is performed.
Methods: We used dissociated cortical and hippocampal neurons coupled to Micro-Electrode Arrays (MEAs) arranged in different configurations characterized by modularity (i.e., the presence of interconnected sub-networks) and heterogeneity (i.e., the co-existence of neurons coming from brain districts). We delivered increasing concentrations of bicuculline (BIC), a neuromodulator acting on the GABAergic system, and we extracted the IC ₅₀ values (i.e., the effective concentration yielding a reduction in the response by 50%) of the mean firing rate for each configuration.
Results: We found significant lower values of the IC ₅₀ computed for modular cortical-hippocampal ensembles than isolated cortical or hippocampal ones.
Discussion: Although tested with a specific neuromodulator, this work aims at proving the relevance of ad hoc experimental models to perform neuropharmacological experiments to avoid errors of overestimation/underestimation leading to biased information in the characterization of the effects of a drug on neuronal networks.
Competing Interests: MB was employed by ScreenNeuroPharm S.r.l. MT was employed by 3Brain GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Brofiga, Poggio, Callegari, Tedesco and Massobrio.)