Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids

Maria-Patapia Zafeiriou (), Guobin Bao, James Hudson, Rashi Halder, Alica Blenkle, Marie-Kristin Schreiber, Andre Fischer, Detlev Schild and Wolfram-Hubertus Zimmermann ()
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Maria-Patapia Zafeiriou: University Medical Center, Georg-August-University
Guobin Bao: University Medical Center, Georg-August-University
James Hudson: University Medical Center, Georg-August-University
Rashi Halder: University of Luxembourg
Alica Blenkle: University Medical Center, Georg-August-University
Marie-Kristin Schreiber: University Medical Center, Georg-August-University
Andre Fischer: University of Göttingen
Detlev Schild: University Medical Center, Georg-August-University
Wolfram-Hubertus Zimmermann: University Medical Center, Georg-August-University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-17521-w

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