期刊
DEVELOPMENT
卷 142, 期 18, 页码 3178-U152出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.123851
关键词
Cerebral cortex; Networks; Neural development; Stem cells; Human
资金
- Cambridge Wellcome Trust PhD programme in Developmental Biology [RG53710]
- Wellcome Trust [092096/Z/10/Z]
- Cancer Research UK [C6946/A14492]
- MRC [MR/L023784/1, MR/L023784/2] Funding Source: UKRI
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 rabiesbased 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.
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