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Stem Cell Reports ; 13(3): 458-473, 2019 09 10.
Article in English | MEDLINE | ID: mdl-31257131

ABSTRACT

The cerebrum is a major center for brain function, and its activity is derived from the assembly of activated cells in neural networks. It is currently difficult to study complex human cerebral neuronal network activity. Here, using cerebral organoids, we report self-organized and complex human neural network activities that include synchronized and non-synchronized patterns. Self-organized neuronal network formation was observed following a dissociation culture of human embryonic stem cell-derived cerebral organoids. The spontaneous individual and synchronized activity of the network was measured via calcium imaging, and subsequent analysis enabled the examination of detailed cell activity patterns, providing simultaneous raster plots, cluster analyses, and cell distribution data. Finally, we demonstrated the feasibility of our system to assess drug-inducible dynamic changes of the network activity. The comprehensive functional analysis of human neuronal networks using this system may offer a powerful tool to access human brain function.


Subject(s)
Brain/metabolism , Calcium/metabolism , Nerve Net/pathology , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Brain/cytology , Cell Culture Techniques , Cell Differentiation , Human Embryonic Stem Cells/cytology , Human Embryonic Stem Cells/metabolism , Humans , Microscopy, Confocal , Nerve Net/drug effects , Nerve Net/metabolism , Organoids/cytology , Organoids/metabolism , Time-Lapse Imaging
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