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Hypoxia has been implicated in a number of central nervous system pathologies including stroke, head trauma and neurodegenerative diseases. Cellular responses to oxygen deprivation are complex and result in activation of short\u2010 and long\u2010term mechanisms to conserve energy and protect cells. Failure of synaptic transmission can be observed within minutes following this hypoxia. The acute effects of hypoxia on synaptic transmission are primarily mediated by altering ion fluxes across membranes, pre\u2010synaptic effects of adenosine and other actions at glutamatergic receptors. A more long\u2010term feature of the response of neurones to hypoxia is the activation of transcription factors such as hypoxia\u2010inducible factor. The activation of hypoxia\u2010inducible factor is governed by a family of dioxygenases called hypoxia\u2010inducible factor prolyl 4 hydroxylases (<jats:styled-content style=\"fixed-case\">PHD<\/jats:styled-content>s). Under hypoxic conditions, <jats:styled-content style=\"fixed-case\">PHD<\/jats:styled-content> activity is inhibited, thereby allowing hypoxia\u2010inducible factor to accumulate and translocate to the nucleus, where it binds to the hypoxia\u2010responsive element sequences of target gene promoters. Inhibition of <jats:styled-content style=\"fixed-case\">PHD<\/jats:styled-content> activity stabilizes hypoxia\u2010inducible factor and other proteins thus acting as a neuroprotective agent. This review will focus on the response of neuronal cells to hypoxia\u2010inducible factor and its targets, including the prolyl hydroxylases. We also present evidence for acute effects of <jats:styled-content style=\"fixed-case\">PHD<\/jats:styled-content> inhibition on synaptic transmission and plasticity in the hippocampus.<\/jats:p>","DOI":"10.1111\/apha.12117","type":"journal-article","created":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T07:49:33Z","timestamp":1369122573000},"page":"298-310","source":"Crossref","is-referenced-by-count":51,"title":["Hypoxia\u2010inducible factor signalling mechanisms in the central nervous system"],"prefix":"10.1111","volume":"208","author":[{"given":"A.","family":"Corcoran","sequence":"first","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science UCD Conway Institute of Biomolecular and Biomedical Research UniversityCollege Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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