RT Journal Article
SR Electronic
T1 Intrinsic network activity in human brain organoids
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.28.428643
DO 10.1101/2021.01.28.428643
A1 Tal Sharf
A1 Tjitse van der Molen
A1 Elmer Guzman
A1 Stella M.K. Glasauer
A1 Gabriel Luna
A1 Zhouwei Cheng
A1 Morgane Audouard
A1 Kamalini G. Ranasinghe
A1 Kiwamu Kudo
A1 Srikantan S. Nagarajan
A1 Kenneth R. Tovar
A1 Linda R. Petzold
A1 Paul K. Hansma
A1 Kenneth S. Kosik
YR 2021
UL http://biorxiv.org/content/early/2021/01/28/2021.01.28.428643.abstract
AB Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiological behavior of neuronal circuits within organoids remains relatively under-explored. With high-density CMOS microelectrode arrays and shank electrodes, we probed broadband and three-dimensional spontaneous activity of human brain organoids. These recordings simultaneously captured local field potentials (LFPs) and single unit activity. From spiking activity, we estimated a directed functional connectivity graph of synchronous neural network activity which showed a large number of weak functional connections enmeshed within a network skeleton of significantly fewer strong connections. Increasing the intrinsic inhibitory tone with a benzodiazepine altered the functional network graph of the organoid by suppressing the network skeleton. Simultaneously examining the spontaneous LFPs and their phase alignment to spiking showed that spike bursts were coherent with theta oscillations in the LFPs. An ensemble of spikes phase-locked to theta frequency oscillations were strongly interconnected as a sub-network within the larger network in which they were embedded. Our results demonstrate that human brain organoids have self-organized neuronal assemblies of sufficient size, cellular orientation, 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 mechanisms, and the effects of external stimuli upon neuronal networks.Competing Interest StatementThe authors have declared no competing interest.