The effect of acute glutamate treatment on the functional connectivity and network topology of cortical cultures

Abstract

Microelectrode arrays (MEAs) allow the investigation of the pharmacological and toxicological effects of chemicals on cultured neuronal networks. Understanding the functional connections between neurons and the resulting neuronal networks is important for evaluating drugs that affect synaptic transmission. Therefore, we acutely treated a mature cultured neuronal network on MEAs with accumulating amounts of glutamate and recorded their altered electrophysiology. Subsequently, a cross-covariance analysis was applied to process the spiking activity in the network and to evaluate the connections between neurons. Finally, graph theory was used to assess the functional network properties under acute glutamate treatment. Our data demonstrated that glutamate increased the similarity, connectivity weight, density, and largest-component size of the functional network. In addition, the small-world network topology was altered after glutamate treatment. Our results indicate that the graph theory can advance our understanding of the pharmacological significance of neurotransmitters on neuronal networks.

Keywords: Connectivity; Glutamate; Graph theory; Microelectrode arrays; Neuronal culture.