Spatiotemporal Mapping of Epileptiform Dynamics in the Hippocampal Circuit via High-Density Biosensors.

70 million people suffer from epilepsy worldwide with temporal lobe epilepsy (TLE) being the most common focal epilepsy in adults. The hippocampus, a region associated with TLE, is highly susceptible to pathological synchronization and epileptogenesis due to its functional and anatomical organization. Despite progress, understanding the distinct contributions of hippocampal subregions to multiplexed activation and hyperactivity remains challenging due to the interplay of receptor dynamics, ion channel regulation, and network synchronization. Here, a large-scale ex-vivo electrophysiological platform was implemented using a high-density CMOS-based biosensor (HD-MEA) to probe the spatiotemporal dynamics of 4AP and ATPA, benchmark compounds for inducing hyperactivity, within the hippocampal circuit. This approach demonstrates the use of large-scale biosensors to address these challenges by enabling high-resolution spatiotemporal mapping of circuit activity, demonstrating their potential to uncover ion channel and receptor-specific spatiotemporal signatures of hyperactivity.