(W1239) CHARACTERISTICS OF ELECTRICAL ACTIVITIES AT SINGLE-CELL RESOLUTION IN HIPSC-DERIVED NEURONS WITH A NOVEL FIELD POTENTIAL IMAGING METHOD ON HD-CMOS-MEA
Professor Tohoku Institute of Technology Sendai, Miyagi, Japan
Abstract: 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, and noninvasive measurements of large areas 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 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. For cultured 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. For cultured human iPSC-derived sensory neurons, we succeeded in classifying neurons with different responses to TRP channel agonists based on single neuron firing patterns. Furthermore, axonal conduction characteristics in each sensory neuron could be analyzed. After administration of anticancer drugs, a decrease in axonal conduction velocity was detected which indicated peripheral neuropathy. Finally, we successfully detected the network activity of brain organoids and assembloids, and extracted the differences from diseased organoids and transitions to compounds. These above results provide new understanding of the basic mechanisms of brain circuits in vitro and ex vivo on human neurological diseases, and show the possibility of the current field potential imaging technology utilization for drug discovery, and compound toxicity assessment.
Funding Source: The grant of collaborative project with Sony semiconductor solutions Inc. Japan Agency for Medical Research and Development (AMED)
