(W1248) Cortical Organoids from Induced Pluripotent Stem Cells Exhibit Spiking and Field Potential Activity Reflective of Sleep-like States and Pharmacological Modulation
Abstract: Cortical organoids derived from human induced pluripotent stem cells (iPSCs) provide a powerful model to study neurodevelopment and network activity. While spiking activity in organoids is well-documented, field potential activity, potentially representing synchronized oscillations akin to in vivo sleep-like states, remains less understood. Pharmacological interventions targeting neural states further expand these models’ potential for studying drug effects on neural circuits. We generated human cortical organoids from iPSCs and assessed their electrophysiological activity using the Biocam Duplex multielectrode array (MEA) platform. We analyzed both spiking and field potential activity to investigate network synchronization. To modulate neural activity, 4-aminopyridine (4AP) was applied to induce small depolarizations, followed by midazolam and xylazine, drugs associated with sleep modulation. Electrophysiological data were analyzed for network-level changes in response to these compounds. Spiking activity emerged by day 120, indicating early network formation and robust field potential activity was observed, demonstrating synchronized oscillatory patterns associated with neural maturation. Following 4AP-induced depolarization, administration of midazolam and xylazine led to significant, expected changes in field potential frequency and amplitude, consistent with their known pharmacodynamic effects. These findings suggest that cortical organoids can recapitulate key neural oscillations, including those linked to sleep-like states. Our study shows that cortical organoids develop spiking and field potential activity, paralleling in vivo network synchronization. The ability to pharmacologically modulate these neural states further supports their physiological relevance. These findings underscore the potential of cortical organoids for investigating neural development, sleep-associated processes, and drug effects on synchronized neural networks.
