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.