RT Journal Article
SR Electronic
T1 Identification of neural oscillations and epileptiform changes in human brain organoids
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 820183
DO 10.1101/820183
A1 Ranmal A. Samarasinghe
A1 Osvaldo A. Miranda
A1 Simon Mitchell
A1 Isabella Ferando
A1 Momoko Watanabe
A1 Jessie E. Buth
A1 Arinnae Kurdian
A1 Peyman Golshani
A1 Kathrin Plath
A1 William E. Lowry
A1 Jack M. Parent
A1 Istvan Mody
A1 Bennett G. Novitch
YR 2019
UL http://biorxiv.org/content/early/2019/10/28/820183.abstract
AB 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.