期刊
CELL STEM CELL
卷 25, 期 4, 页码 558-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2019.08.002
关键词
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资金
- California Institute for Regenerative Medicine (CIRM) [DISC1-08825, DISC2-09649]
- NIH [R01MH108528, R01MH094753, R01MH109885, R01MH100175, R56MH109587]
- SFARI [345469]
- NARSAD Independent Investigator Grant
- Sloan Research Fellowship
- Whitehall Foundation [2017-12-73]
- National Science Foundation [1736028]
- National Institutes of Health NIH/NIGMS [K12 GM068524]
- National Cooperative Reprogrammed Cell Research Groups (NCRCRG) [U19MH1073671]
- Natural Sciences and Engineering Research Council of Canada (NSERC PGS-D)
- UCSD Kavli Innovative Research Grant (IRG)
- Frontiers for Innovation Scholars Program
- UC San Diego School of Medicine
- Direct For Social, Behav & Economic Scie
- Division Of Behavioral and Cognitive Sci [1736028] Funding Source: National Science Foundation
Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed human cortical organoids that dynamically change cellular populations during maturation and exhibited consistent increases in electrical activity over the span of several months. The spontaneous network formation displayed periodic and regular oscillatory events that were dependent on glutamatergic and GABAergic signaling. The oscillatory activity transitioned to more spatiotemporally irregular patterns, and synchronous network events resembled features similar to those observed in preterm human electroencephalography. These results show that the development of structured network activity in a human neocortex model may follow stable genetic programming. Our approach provides opportunities for investigating and manipulating the role of network activity in the developing human cortex.
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