Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development
Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development
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DOI：
10.1016/j.stem.2019.08.002
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发表时间：
2019-10-03
期刊：
影响因子：
23.9
通讯作者：
Muotri, Alysson R.
中科院分区：
文献类型：
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作者：
Trujillo, Cleber A.;Gao, Richard;Muotri, Alysson R.
早期脑成熟过程中的结构和转录变化遵循遗传学定义的固定发育程序。然而，对于功能性网络活动是否如此仍然未知，主要是由于实验无法进入活体人脑的初始阶段。在这里，我们开发了人类皮质类器官，它们在成熟过程中动态地改变细胞群体，并在几个月的时间内表现出电活动的一致增加。自发网络的形成显示出依赖于谷氨酸能和GABA能信号的周期性和规则的振荡事件。振荡活动过渡到更多的时空不规则的模式，和同步网络事件类似的功能，在早产儿的人类脑电图观察到的。这些结果表明，人类新皮层模型中结构化网络活动的发展可能遵循稳定的遗传编程。我们的方法为研究和操纵网络活动在人类大脑皮层发育中的作用提供了机会。
Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed human cortical organoids that dynamically change cellular populations during maturation and exhibited consistent increases in electrical activity over the span of several months. The spontaneous network formation displayed periodic and regular oscillatory events that were dependent on glutamatergic and GABAergic signaling. The oscillatory activity transitioned to more spatiotemporally irregular patterns, and synchronous network events resembled features similar to those observed in preterm human electroencephalography. These results show that the development of structured network activity in a human neocortex model may follow stable genetic programming. Our approach provides opportunities for investigating and manipulating the role of network activity in the developing human cortex.