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, 25 (4), 558-569.e7

Complex Oscillatory Waves Emerging From Cortical Organoids Model Early Human Brain Network Development

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Complex Oscillatory Waves Emerging From Cortical Organoids Model Early Human Brain Network Development

Cleber A Trujillo et al. Cell Stem Cell.

Abstract

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.

Keywords: cortical organoids; network oscillations; phase-amplitude coupling; preterm electroencephalography; single-cell transcriptomics; stem cells.

Conflict of interest statement

DECLARATION OF INTERESTS

Dr. Muotri is a co-founder and has equity interest in TISMOO, a company dedicated to genetic analysis focusing on therapeutic applications customized for autism spectrum disorder and other neurological disorders with genetic origins. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies.

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