Functional neuronal circuitry and oscillatory dynamics in human brain organoids

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, Kenneth R. Tovar, Linda R. Petzold, Andreas Hierlemann, Paul K. Hansma and Kenneth S. Kosik ()
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Tal Sharf: University of California Santa Barbara
Tjitse Molen: University of California Santa Barbara
Stella M. K. Glasauer: University of California Santa Barbara
Elmer Guzman: University of California Santa Barbara
Alessio P. Buccino: ETH Zürich
Gabriel Luna: University of California Santa Barbara
Zhuowei Cheng: University of California Santa Barbara
Morgane Audouard: 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
Kenneth S. Kosik: University of California Santa Barbara

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32115-4

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DOI: 10.1038/s41467-022-32115-4

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