Pharmacological manipulation of nested oscillations in human iPSC-derived 2D neuronal networks

Authors: Deborah Pré, Christian Cazares, Alexander T. Wooten, Haowen Zhou, Isabel Onofre, Ashley Neil, Todd Logan, Ruilong Hu, Jan H. Lui, Bradley Voytek, and Anne G. Bang

Neurobiology of Disease, 24 January 2026

Scientists use the Maestro MEA platform to explore the mechanisms behind oscillogenesis in human neural networks. 

Synchronized oscillatory bursts play a central role in shaping functional brain networks, driving both the formation and dissolution of large-scale neuronal connectivity. However, the cellular and molecular mechanisms underlying oscillogenesis—the emergence of coordinated rhythmic activity—remain poorly understood. In this study, researchers investigated how nested oscillations arise and evolve across developing human neural networks

Using the Maestro MEA platform, the team recorded network activity in 2D neural cultures at multiple developmental stages and following pharmacological perturbations. They observed synchronized oscillatory bursts spanning large neuronal populations and identified a critical role for GABAergic neurons in the formation and maintenance of nested oscillations. Further experiments revealed that voltage-gated potassium channels and cholinergic receptor signaling modulate oscillatory dynamics, providing insight into how intrinsic excitability and neuromodulatory pathways shape network rhythms. 

Together, these findings advance our understanding of how complex neural oscillations emerge in vitro and highlight the value of human-relevant MEA models for studying the mechanisms that organize large-scale brain network activity.