Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids
| Autor: | Zafeiriou, Maria-Patapia, Bao, Guobin, Hudson, James, Halder, Rashi, Blenkle, Alica, Schreiber, Marie-Kristin, Fischer, Andre, Schild, Detlev, Zimmermann, Wolfram-Hubertus |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Biotechnologie [F06] [Sciences du vivant]
Science Neurogenesis Induced Pluripotent Stem Cells Cell Culture Techniques Action Potentials Developmental neurogenesis Article physiology [Action Potentials] Biotechnology [F06] [Life sciences] physiology [Neuronal Plasticity] Humans metabolism [gamma-Aminobutyric Acid] lcsh:Science gamma-Aminobutyric Acid Neurons Neuronal Plasticity Tissue Engineering cytology [Brain] growth & development [Brain] physiology [Organoids] Brain Cell Differentiation physiology [Neurons] methods [Tissue Engineering] Organoids nervous system lcsh:Q ddc:500 physiology [Induced Pluripotent Stem Cells] |
| Zdroj: | Nature Communications Nature Communications 11(1), 3791 (2020). doi:10.1038/s41467-020-17521-w Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-17521-w |
| Popis: | 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. Brain organoids are important tools to study early development and disease but little is known of their network activity and plasticity. Here the authors generate iPSC-derived neuronal organoids that display early network formation and maturation with evidence for a GABA polarity switch and long-term potentiation. |
| Databáze: | OpenAIRE |
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