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

Abstract

IntroductionThe 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.MethodsWe 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 IC50 values (i.e., the effective concentration yielding a reduction in the response by 50%) of the mean firing rate for each configuration.ResultsWe found significant lower values of the IC50 computed for modular cortical-hippocampal ensembles than isolated cortical or hippocampal ones.DiscussionAlthough 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.

Electrical and chemical modulation of homogeneous and heterogeneous human-iPSCs-derived neuronal networks on high density arrays

“…The human brain is characterized by several complex features that are pivotal for creating a faithful in vitro model of its functioning. These features encompass integration, modulation, three-dimensionality, and most importantly, heterogeneity ( Brofiga et al, 2023 ). Heterogeneity, in this context, entails the existence of a variety of different neurons with distinct characteristics and functions.…”