A Comparison of the Application of Four MEA-Based Neurotoxicity Screening Methods in Ni²⁺ Neurotoxicity Assessment

Microelectrode array (MEA) technology is widely employed in electrophysiological research and, in recent years, has increasingly been applied in the screening of neurotoxicity. In this study, we investigated the neurotoxic effects of different concentrations of Ni²⁺ by analyzing its influence on the mean firing and bursting rates of spontaneous activity, as well as the frequency of electrical-stimulation-evoked activity in the neocortical region in rat brain slices through MEA. Integrating our team's prior findings on Ni²⁺'s influence on the electrical stimulation threshold of evoked activity, we compared the application effectiveness of the four MEA-based neurotoxicity screening methods in Ni²⁺ neurotoxicity research. Our results demonstrate that all of these methods can effectively assess the neurotoxic effects of Ni²⁺; however, they differ in certain aspects, such as the applicable neuronal networks and data-processing approaches. We also found that Ni²⁺ influences spontaneous and electrical-stimulation-evoked activity in the neocortical region in rat brain slices via distinct mechanisms.