Julia Izsak, Stephan Theiss, Sebastian Illes
Abstract
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.