Ontogeny of oscillatory slow-wave and neuronal population activity in human iPSC-3D cortical circuits

Oscillatory slow-wave activity (0.5--100 Hz) emerges during fetal human cortex development reflecting functional consequences of cellular brain ontogeny. Human induced pluripotent stem cell-derived (iPSC) neural in vitro models recapitulate aspects of in vivo cellular brain ontogeny, while neuronal mesoscale functional ontogeny is largely uncharacterized. We utilized a human iPSC-derived 3D cortical aggregate model to assess properties of emerging oscillatory slow-wave activity and its relation to synchronous neuronal population activity in cortical circuits. We reveal that oscillatory slow-wave activity (< 1 Hz), phased locked to synchronous population bursting, emerges within 14 days in vitro followed by consecutive stages of emerging delta (1--4 Hz), theta (4--11 Hz), beta (11--30 Hz), and gamma (30--55 Hz) oscillatory activity, accompanied by stage-specific changes in neuronal population burst pattern characteristics. We provide a classification of neuronal mesoscale functional ontogeny stages of developing human iPSC-cortical circuits, where each stage is defined by specific oscillatory slow-wave activity and characteristic synchronous neuronal bursting patterns.