The emergence of electrical activity in human brain organoids

Human brain organoids, generated from pluripotent stem cells, recapitulate fundamental features of human brain development, including neuronal diversity, regional architecture, and functional network activity. Integrated multimodal and transcriptomic analyses reveal a molecular repertoire of ionotropic receptors supporting action potentials, synaptic transmission, and oscillatory dynamics resembling early brain activity. This review synthesizes current knowledge on the molecular and electrophysiological determinants of neuronal maturation and network computations, from synaptic integration to large-scale dynamics. Ongoing refinements in organoid generation are improving developmental timing and structural fidelity, establishing these models as powerful platforms for investigating brain differentiation, circuit formation, disease mechanisms, and biomedical applications.