Identification of neural oscillations and epileptiform changes in human brain organoids

R.A. Samarasinghe, O. Miranda, S. Mitchell, I. Ferando, M. Watanabe, J.E. Buth, A. Kurdian, P. Golshani, K. Plath, W.E. Lowry, J.M. Parent, I. Mody, B.G. Novitch, BioRxiv (2019).

Preprint | Published | English
Author
; ; ; ; ; ; ; ; ; ; ;
All
Abstract
Human brain organoids represent a powerful tool for the study of human neurological diseases particularly those that impact brain growth and structure. However, many neurological diseases lack obvious anatomical abnormalities, yet significantly impact neural network functions, raising the question of whether organoids possess sufficient neural network architecture and complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex oscillatory network behaviors reminiscent of intact brain preparations. We further demonstrate strikingly abnormal epileptiform network activity in organoids derived from a Rett Syndrome patient despite only modest anatomical differences from isogenically matched controls, and rescue with an unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide an essential foundation for the utilization of human brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.
Publishing Year
Date Published
2019-10-28
Journal Title
bioRxiv
Page
34
IST-REx-ID

Cite this

Samarasinghe RA, Miranda O, Mitchell S, et al. Identification of neural oscillations and epileptiform changes in human brain organoids. bioRxiv. 2019.
Samarasinghe, R. A., Miranda, O., Mitchell, S., Ferando, I., Watanabe, M., Buth, J. E., … Novitch, B. G. (2019). Identification of neural oscillations and epileptiform changes in human brain organoids. BioRxiv. Cold Spring Harbor Laboratory.
Samarasinghe, Ranmal A., Osvaldo Miranda, Simon Mitchell, Isabella Ferando, Momoko Watanabe, Jessie E. Buth, Arinnae Kurdian, et al. “Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids.” BioRxiv. Cold Spring Harbor Laboratory, 2019.
R. A. Samarasinghe et al., “Identification of neural oscillations and epileptiform changes in human brain organoids,” bioRxiv. Cold Spring Harbor Laboratory, 2019.
Samarasinghe RA, Miranda O, Mitchell S, Ferando I, Watanabe M, Buth JE, Kurdian A, Golshani P, Plath K, Lowry WE, Parent JM, Mody I, Novitch BG. 2019. Identification of neural oscillations and epileptiform changes in human brain organoids. bioRxiv.
Samarasinghe, Ranmal A., et al. “Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids.” BioRxiv, Cold Spring Harbor Laboratory, 2019.

Link(s) to Main File(s)
Access Level
OA Open Access

Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar