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In the present study, we instead focus on plasticity in mature neurons in the neocortex of adult animals. We find that the glutamate receptor 1 (GluR1) subunit of the AMPA receptor is involved in experience-dependent plasticity in adult cortex<jats:italic>in vivo<\/jats:italic>and that it acts in addition to neuronal nitric oxide synthase (\u03b1NOS1), an enzyme that produces the rapid synaptic signaling molecule nitric oxide (NO). Potentiation of the spared whisker response, following single whisker experience, is \u223c33% less in GluR1-null mutants than in wild types. We found that the remaining plasticity depended on \u03b1NOS1. Potentiation was reduced by &gt;42% in the single \u03b1NOS1-null mutants and completely abolished in GluR1\/\u03b1NOS1 double-knock-out mice. However, potentiation in GluR1\/NOS3 double knock-outs occurred at similar levels to that seen in GluR1 single knock-outs. Synaptic plasticity in the layer IV to II\/III pathway<jats:italic>in vitro<\/jats:italic>mirrored the results<jats:italic>in vivo<\/jats:italic>, in that LTP was present in GluR1\/NOS3 double-knock-out mice but not in the GluR1\/\u03b1NOS1 animals. While basal levels of NO in cortical slices depended on both \u03b1NOS1 and NOS3, NMDA receptor-dependent NO release only depended on \u03b1NOS1 and not on NOS3. These findings demonstrate that \u03b1NOS1 acts in concert with GluR1 to produce experience-dependent plasticity in the neocortex.<\/jats:p>","DOI":"10.1523\/jneurosci.1590-11.2011","type":"journal-article","created":{"date-parts":[[2011,8,3]],"date-time":"2011-08-03T23:48:44Z","timestamp":1312415324000},"page":"11220-11230","source":"Crossref","is-referenced-by-count":33,"title":["Experience-Dependent Plasticity Acts via GluR1 and a Novel Neuronal Nitric Oxide Synthase-Dependent Synaptic Mechanism in Adult Cortex"],"prefix":"10.1523","volume":"31","author":[{"given":"James","family":"Dachtler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Hardingham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislaw","family":"Glazewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas 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