Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.
Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.
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DOI：
10.1242/dev.123851
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发表时间：
2015-09-15
期刊：
影响因子：
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通讯作者：
Livesey FJ
中科院分区：
文献类型：
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作者：
Kirwan P;Turner-Bridger B;Peter M;Momoh A;Arambepola D;Robinson HP;Livesey FJ
神经系统发育的一个关键方面，包括大脑皮层，是高阶神经网络的形成。神经网络的发展经历了几个阶段，在体内具有不同的活动模式，这被认为是修剪和微调网络连接。我们在这里报道，人类多能干细胞(HPSC)来源的大脑皮层神经元形成大规模网络，反映在体内发育中的大脑皮层中发现的那些网络。在培养的几周内，同步振荡网络以一种高度刻板的模式发展。在产生非同步、有序的活动模式之前，振荡频率增加的初始阶段之后是频率降低的阶段。HPSC来源的皮质神经网络是兴奋性的，由AMPA和NMDA型谷氨酸受体激活驱动，并可以经历NMDA型受体介导的可塑性。通过使用狂犬病的跨突触追踪研究PSC来源的培养中的单个神经元连接，我们发现了两大类神经元连接：大多数神经元具有少量的突触前输入(<；10)，而少数中枢样神经元具有大量的突触连接(>；40)。这些数据表明，hPSC来源的皮质网络的形成模拟了体内皮质网络的发育和功能，证明了体外系统在人类前脑神经网络生物学的机制研究中的应用。摘要：人类PSC来源的大脑皮层神经元形成大规模的功能网络，随着时间的推移而变化，并模仿体内发育中的大脑皮层的神经网络。
A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. Summary: Human PSC-derived cerebral cortex neurons form large-scale functional networks that change over time and mimic those found in the developing cerebral cortex in vivo.