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Cell Stem Cell. 2019 Aug 23. pii: S1934-5909(19)30337-6. doi: 10.1016/j.stem.2019.08.002. [Epub ahead of print]

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

Author information

1
Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
2
Neurosciences Graduate Program, Institute for Neural Computation, Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92093, USA.
3
Center for Epigenomics, Department of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
4
Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
5
Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
6
Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
7
Department of Radiology, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
8
Department of Radiology, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
9
Neurosciences Graduate Program, Institute for Neural Computation, Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92093, USA; Kavli Institute for Brain and Mind and Halıcıoğlu Data Science Institute, University of California, San Diego, La Jolla, CA 92093, USA.
10
Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Kavli Institute for Brain and Mind and Halıcıoğlu Data Science Institute, University of California, San Diego, La Jolla, CA 92093, USA; Center for Academic Research and Training in Anthropogeny (CARTA), La Jolla, CA 92093, USA. Electronic address: muotri@ucsd.edu.

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

PMID:
31474560
DOI:
10.1016/j.stem.2019.08.002

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