MAPPING ELECTRICAL ACTIVITY OF NEURONAL NETWORKS AT SINGLE-CELL RESOLUTION USING A NOVEL UHD-CMOS MEA FIELD-POTENTIAL IMAGING

The technology for measuring the electrical activity of the nervous system is essential for understanding neurological diseases, drug discovery development, and toxicity evaluation of compounds. Recent development of microelectrode array (MEA) with large amounts of electrodes at a high density provides a high spatio-temporal resolution at the single-cell level, which increase insights on underlying neuronal function. In the present study, we used a HD-CMOS-MEA with 236,880 electrodes covering a wide sensing area in presenting a detailed and single-cell-level neural activity analysis platform.
Samples of human iPSC-derived cortical neurons, sensory neurons, and human brain organoids were prepared on the UHD-CMOS-MEA and the electrophysiological activity were measured before and after drug administration. A novel field potential imaging analysis was performed with optimization upon different samples. Using human iPSC-derived cortical neurons, field potential imaging analysis revealed that the synaptic strength was influenced by compounds based on single-cell time-series patterns. With both network neural analysis parameters and single neuron analysis parameters, several novel information in evaluating the drug responsiveness of neural networks was revealed successfully. Using human iPSC-derived sensory neurons, axonal conduction characteristics in each sensory neuron were successfully traced. After administration of anticancer drugs, a decrease in axonal conduction velocity was detected which indicated peripheral neuropathy. Finally, network activities and transition to compounds were successfully extracted for brain organoids.
These results provide new understanding of the basic mechanisms on human neurological diseases, and show the possibility of the current field potential imaging technology utilization for drug discovery, and compound toxicity assessment.