Developmental GABA Polarity Switch and Neuronal Plasticity in Bioengineered Neuronal Organoids

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jul 31

PMID 32728089

Citations 59

Authors

Maria-Patapia Zafeiriou

Guobin Bao

James Hudson

Rashi Halder

Alica Blenkle

Marie-Kristin Schreiber

Andre Fischer

Detlev Schild

Wolfram-Hubertus Zimmermann

Affiliations

Soon will be listed here.

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.

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