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Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids

Author

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  • Maria-Patapia Zafeiriou

    (University Medical Center, Georg-August-University
    DZHK (German Center for Cardiovascular Research), partner site Göttingen
    University of Göttingen)

  • Guobin Bao

    (University Medical Center, Georg-August-University
    DZHK (German Center for Cardiovascular Research), partner site Göttingen
    University Medical Center, Georg-August-University)

  • James Hudson

    (University Medical Center, Georg-August-University
    DZHK (German Center for Cardiovascular Research), partner site Göttingen
    QIMR Berghofer Medical Research Institute)

  • Rashi Halder

    (University of Luxembourg
    German Center for Neurodegenerative Diseases (DZNE) Goettingen)

  • Alica Blenkle

    (University Medical Center, Georg-August-University)

  • Marie-Kristin Schreiber

    (University Medical Center, Georg-August-University)

  • Andre Fischer

    (University of Göttingen
    German Center for Neurodegenerative Diseases (DZNE) Goettingen
    University Medical Center, Georg-August-University)

  • Detlev Schild

    (University Medical Center, Georg-August-University)

  • Wolfram-Hubertus Zimmermann

    (University Medical Center, Georg-August-University
    DZHK (German Center for Cardiovascular Research), partner site Göttingen
    University of Göttingen)

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.

Suggested Citation

  • Maria-Patapia Zafeiriou & Guobin Bao & James Hudson & Rashi Halder & Alica Blenkle & Marie-Kristin Schreiber & Andre Fischer & Detlev Schild & Wolfram-Hubertus Zimmermann, 2020. "Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17521-w
    DOI: 10.1038/s41467-020-17521-w
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