{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:51:48Z","timestamp":1792713108726,"version":"4.5.0"},"reference-count":72,"publisher":"Society for Neuroscience","issue":"4","license":[{"start":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T00:00:00Z","timestamp":1090972800000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2004,1,28]]},"abstract":"<jats:p>The regulated delivery of AMPA-type glutamate receptors (AMPARs) to synapses is an important mechanism underlying synaptic plasticity. Here, we ask whether the synaptic scaffolding protein PSD-95 (postsynaptic density 95) participates in AMPAR incorporation during two forms of synaptic plasticity. In hippocampal slice cultures, the expression of PSD-95\u2013green fluorescent protein (PSD-95\u2013GFP) increases AMPAR currents by selectively delivering glutamate receptor 1 (GluR1)-containing receptors to synapses, thus mimicking long-term potentiation (LTP). Mutational analysis shows that the N terminal of PSD-95 including the first two PDZ [PSD-95\/Discs large (Dlg)\/zona occludens-1 (ZO-1)] domains is necessary and sufficient to mediate this effect. Further supporting a role in synaptic plasticity, wild-type PSD-95 occludes LTP and dominant negative forms block LTP. Moreover, we demonstrate that PSD-95 also participates in AMPAR delivery during experience-driven plasticity<jats:italic>in vivo<\/jats:italic>. In the barrel cortex from experience-deprived animals, the expression of PSD-95\u2013GFP selectively increases AMPAR currents, mimicking experience-driven plasticity. In nondeprived animals, PSD-95\u2013GFP produces no additional potentiation, indicating common mechanisms between PSD-95-mediated potentiation and experience-driven synaptic strengthening. A dominant negative form of PSD-95 blocks experience-driven potentiation of synapses. Pharmacological analysis in slice cultures reveals that PSD-95 acts downstream of other signaling pathways involved in LTP. We conclude that PSD-95 controls activity-dependent AMPAR incorporation at synapses via PDZ interactions not only during LTP<jats:italic>in vitro<\/jats:italic>but also during experience-driven synaptic strengthening by natural stimuli<jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1523\/jneurosci.4733-03.2004","type":"journal-article","created":{"date-parts":[[2004,1,29]],"date-time":"2004-01-29T03:23:41Z","timestamp":1075346621000},"page":"916-927","source":"Crossref","is-referenced-by-count":513,"title":["Postsynaptic Density 95 controls AMPA Receptor Incorporation during Long-Term Potentiation and Experience-Driven Synaptic 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