Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids
Year: 2020
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,478
Funders: Deutsches Zentrum für Herz-Kreislaufforschung, Deutsche Forschungsgemeinschaft, Deutsches Zentrum für Neurodegenerative Erkrankungen, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Center for Advancing Translational Sciences, Common Fund
Awards: G1705230701, G1746494712, G2092439215, G3338680746, G3445732291, G3809509723, G3938096678, G4552007757, G5131877326, G53548256, G584537252, EXC 2067: Multiscale Bioimaging: Von molekularen Maschinen zu Netzwerken erregbarer Zellen, G6846689705, G700915580, G7032381815, G756744335, G7659843029, G7987891391
OpenAlex ID: W3045516111