Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids
Zafeiriou, Maria-Patapia ; Bao, Guobin ; Hudson, James ; Halder, Rashi ; Blenkle, Alica ; Schreiber, Marie-Kristin ; Fischer, Andre ; Schild, Detlev et al.
Citable Link (URL):http://resolver.sub.uni-goettingen.de/purl?gs-1/17472
Brain organoids are promising tools for disease modeling and drug development. For proper neuronal network formation excitatory and inhibitory neurons as well as glia need to co-develop. Here, we report the directed self-organization of human induced pluripotent stem cells in a collagen hydrogel towards a highly interconnected neuronal network at a macroscale tissue format. Bioengineered Neuronal Organoids (BENOs) comprise interconnected excitatory and inhibitory neurons with supportive astrocytes and oligodendrocytes. Giant depolarizing potential (GDP)-like events observed in early BENO cultures mimic early network activity of the fetal brain. The observed GABA polarity switch and reduced GDPs in >40 day BENO indicate progressive neuronal network maturation. BENOs demonstrate expedited complex network burst development after two months and evidence for long-term potentiation. The similarity of structural and functional properties to the fetal brain may allow for the application of BENOs in studies of neuronal plasticity and modeling of disease.
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