Samarasinghe_Manuscript_Final_Complete.pdf (26.68 MB)
Identification of neural oscillations and epileptiform changes in human brain organoids
journal contribution
posted on 2023-06-10, 01:10 authored by Ranmal A Samarasinghe, Osvaldo A Miranda, Jessie E Buth, Simon MitchellSimon Mitchell, Isabella Ferando, Momoko Watanabe, Thomas F Allison, Arinnae Kurdian, Namie N Fotion, Michael J Gandal, Peyman Golshani, Kathrin Plath, William E Lowry, Jack M Parent, Istvan Mody, Bennett G NovitchBrain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network 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 network dynamics reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from induced pluripotent stem cells from individuals with Rett syndrome, accompanied by transcriptomic differences revealed by single-cell analyses. We also rescue key physiological activities with an unconventional neuroregulatory drug, pifithrin-a. Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.
History
Publication status
- Published
File Version
- Accepted version
Journal
Nature NeuroscienceISSN
1097-6256Publisher
Nature ResearchExternal DOI
Volume
24Page range
1488-1500Event location
United StatesDepartment affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-09-28First Open Access (FOA) Date
2022-02-24First Compliant Deposit (FCD) Date
2021-09-27Usage metrics
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