Predicting in vitro single-neuron firing rates upon pharmacological perturbation using Graph Neural Networks

Modern Graph Neural Networks (GNNs) provide opportunities to study the determinants underlying the complex activity patterns of biological neuronal networks. In this study, we applied GNNs to a large-scale electrophysiological dataset of rodent primary neuronal networks obtained by means of high-density microelectrode arrays (HD-MEAs). HD-MEAs allow for long-term recording of extracellular spiking activity of individual neurons and networks and enable the extraction of physiologically relevant features at the single-neuron and population level. We employed established GNNs to generate a combined representation of single-neuron and connectivity features obtained from HD-MEA data, with the ultimate goal of predicting changes in single-neuron firing rate induced by a pharmacological perturbation. The aim of the main prediction task was to assess whether single-neuron and functional connectivity features, inferred under baseline conditions, were informative for predicting changes in neuronal activity in response to a perturbation with Bicuculline, a GABA(A) receptor antagonist. Our results suggest that the joint representation of node features and functional connectivity, extracted from a baseline recording, was informative for predicting firing rate changes of individual neurons after the perturbation. Specifically, our implementation of a GNN model with inductive learning capability (GraphSAGE) outperformed other prediction models that relied only on single-neuron features. We tested the generalizability of the results on two additional datasets of HD-MEA recordings–a second dataset with cultures perturbed with Bicuculline and a dataset perturbed with the GABA(A) receptor antagonist Gabazine. GraphSAGE models showed improved prediction accuracy over other prediction models. Our results demonstrate the added value of taking into account the functional connectivity between neurons and the potential of GNNs to study complex interactions between neurons.