Pharmacological Responses in Cultured Human iPSC-Derived Cortical Neurons Using Multi-Electrode Array

Human induced pluripotent stem cell (hiPSC)-derived neurons may be used effectively for drug discovery and cell-based therapy. However, this is limited by the immaturity of cultured hiPSC-derived neurons and the lack of established functional evaluation methods. We used a multi-electrode array (MEA) system to investigate the effects of co-culturing astrocytes with hiPSC-derived cortical neurons on long-term culture, spontaneous firing activity, and drug responsiveness. The co-culture facilitated long-term culture of hiPSC-derived neurons over 400 days. Long-term spontaneous firing activity was also observed. After >3 months in culture, we observed synchronous burst firing activity due to synapse transmission within neuronal networks. Compared with rat neurons, hiPSC-derived neurons required a longer time to mature functionally. In drug response studies, addition of the synapse antagonist bicuculline, CNQX and AP5, and the agonist, L-glutamate, a kainic acid, induced significant changes in the firing rate and synchronised burst firing patterns. Furthermore, administration of pentylentetrazole (PTZ) induced epileptiform activity. Anti-epilepsy drugs, phenytoin and sodium valproate, reduced epileptiform activity. These results suggest that long-term electrophysiological measurements in hiPSC-derived neurons using an MEA system may be beneficial for clarifying the functions of human neuronal circuits and drug screening applications.