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However, how these oligomers might first impair neuronal function at the onset of pathology is poorly understood. Here we have examined the underlying toxic effects caused by an increase in levels of intracellular A\u03b2, an event that could be important during the early stages of the disease. We show that oligomerised A\u03b2 induces a rapid enhancement of AMPA receptor-mediated synaptic transmission (EPSC<jats:sub>A<\/jats:sub>) when applied intracellularly. This effect is dependent on postsynaptic Ca<jats:sup>2+<\/jats:sup>and PKA. Knockdown of GluA1, but not GluA2, prevents the effect, as does expression of a S845-phosphomutant of GluA1. Significantly, an inhibitor of Ca<jats:sup>2+<\/jats:sup>-permeable AMPARs (CP-AMPARs), IEM 1460, reverses the increase in the amplitude of EPSC<jats:sub>A<\/jats:sub>. These results suggest that a primary neuronal response to intracellular A\u03b2 oligomers is the rapid synaptic insertion of CP-AMPARs.<\/jats:p>","DOI":"10.1038\/srep10934","type":"journal-article","created":{"date-parts":[[2015,6,9]],"date-time":"2015-06-09T16:05:11Z","timestamp":1433865911000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus"],"prefix":"10.1038","volume":"5","author":[{"given":"Daniel J.","family":"Whitcomb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen L.","family":"Hogg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Regan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Piers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Narayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry","family":"Whitehead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryony L.","family":"Winters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunjoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"St George-Hyslop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Klenerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham L.","family":"Collingridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihoon","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangwook","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,6,9]]},"reference":[{"key":"BFsrep10934_CR1","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/j.neuron.2014.05.004","volume":"82","author":"TL Spires-Jones,","year":"2014","unstructured":"Spires-Jones, T. 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