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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 (&amp;lt;10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (&amp;gt;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.<\/jats:p>","DOI":"10.1242\/dev.123851","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T11:47:36Z","timestamp":1442922456000},"page":"3178-3187","source":"Crossref","is-referenced-by-count":115,"title":["Development and function of human cerebral cortex neural networks from pluripotent stem cells <i>in vitro<\/i>"],"prefix":"10.1242","volume":"142","author":[{"given":"Peter","family":"Kirwan","sequence":"first","affiliation":[{"name":"Wellcome Trust\/CRUK Gurdon Institute and\u2008Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benita","family":"Turner-Bridger","sequence":"additional","affiliation":[{"name":"Wellcome Trust\/CRUK Gurdon Institute and\u2008Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Peter","sequence":"additional","affiliation":[{"name":"Wellcome Trust\/CRUK Gurdon Institute and\u2008Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayiba","family":"Momoh","sequence":"additional","affiliation":[{"name":"Wellcome Trust\/CRUK Gurdon Institute and\u2008Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devika","family":"Arambepola","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh P. 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