类有机物
神经科学
诱导多能干细胞
人脑
神经网络
生物
药物发现
生物神经网络
神经影像学
新皮层
皮质(解剖学)
生物信息学
胚胎干细胞
生物化学
基因
作者
Ranmal A. Samarasinghe,Osvaldo A. Miranda,Jessie E. Buth,Simon 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,István Módy,Bennett G. Novitch
标识
DOI:10.1038/s41593-021-00906-5
摘要
Brain 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-α. 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.
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