In this study, the directed self-organization of human induced pluripotent stem cells towards a highly interconnected neuronal network is reported. The described bioengineered neuronal organoids (BENOs) consist of functionally integrated excitatory and inhibitory neurons as well as supporting glia. Giant depolarizing potential (GDP)-like events observed in early BENO cultures mimic early network activity of the fetal brain. The observed reduction of GDPs in > 40-day BENOs indicates progressive neuronal network maturation.
Collectively, BENOs demonstrate neuronal network function classically found in the developing brain, such as GDP, and within the more matured human brain, such as neuronal plasticity. The similarity of structural and functional properties to the fetal brain may allow for the application of BENOs in studies of neuronal plasticity and modelling of diseases as well as in drug development.
Developmental GABA polarity switch and neuronal plasticity in bioengineered neuronal organoids
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