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Functional neuronal circuitry and oscillatory dynamics in human brain organoids

Author

Listed:
  • Tal Sharf

    (University of California Santa Barbara
    University of California Santa Barbara
    University of California Santa Cruz)

  • Tjitse Molen

    (University of California Santa Barbara
    University of California Santa Barbara)

  • Stella M. K. Glasauer

    (University of California Santa Barbara
    University of California Santa Barbara)

  • Elmer Guzman

    (University of California Santa Barbara
    University of California Santa Barbara)

  • Alessio P. Buccino

    (ETH Zürich)

  • Gabriel Luna

    (University of California Santa Barbara
    University of California Santa Barbara)

  • Zhuowei Cheng

    (University of California Santa Barbara)

  • Morgane Audouard

    (University of California Santa Barbara
    University of California Santa Barbara)

  • Kamalini G. Ranasinghe

    (University of California San Francisco)

  • Kiwamu Kudo

    (University of California San Francisco)

  • Srikantan S. Nagarajan

    (University of California San Francisco)

  • Kenneth R. Tovar

    (University of California Santa Barbara)

  • Linda R. Petzold

    (University of California Santa Barbara)

  • Andreas Hierlemann

    (ETH Zürich)

  • Paul K. Hansma

    (University of California Santa Barbara
    University of California Santa Barbara)

  • Kenneth S. Kosik

    (University of California Santa Barbara
    University of California Santa Barbara)

Abstract

Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiology of neuronal circuits within organoids remains under-explored. With high-density CMOS microelectrode arrays and shank electrodes, we captured spontaneous extracellular activity from brain organoids derived from human induced pluripotent stem cells. We inferred functional connectivity from spike timing, revealing a large number of weak connections within a skeleton of significantly fewer strong connections. A benzodiazepine increased the uniformity of firing patterns and decreased the relative fraction of weakly connected edges. Our analysis of the local field potential demonstrate that brain organoids contain neuronal assemblies of sufficient size and functional connectivity to co-activate and generate field potentials from their collective transmembrane currents that phase-lock to spiking activity. These results point to the potential of brain organoids for the study of neuropsychiatric diseases, drug action, and the effects of external stimuli upon neuronal networks.

Suggested Citation

  • Tal Sharf & Tjitse Molen & Stella M. K. Glasauer & Elmer Guzman & Alessio P. Buccino & Gabriel Luna & Zhuowei Cheng & Morgane Audouard & Kamalini G. Ranasinghe & Kiwamu Kudo & Srikantan S. Nagarajan &, 2022. "Functional neuronal circuitry and oscillatory dynamics in human brain organoids," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32115-4
    DOI: 10.1038/s41467-022-32115-4
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    References listed on IDEAS

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    1. Tatsuya Osaki & Tomoya Duenki & Siu Yu A. Chow & Yasuhiro Ikegami & Romain Beaubois & Timothée Levi & Nao Nakagawa-Tamagawa & Yoji Hirano & Yoshiho Ikeuchi, 2024. "Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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