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Evidently, synapses in sensory systems such as auditory brainstem circuits mature rapidly to achieve high-fidelity neurotransmission for sound localization. This depends on a developmental switch in AMPAR composition from slow-gating GluA1-dominant to fast-gating GluA4-dominant, but the mechanisms underlying this switch remain unknown. We hypothesize that patterned stimuli mimicking spontaneous\/sound evoked activity in the early postnatal stage drives this gating switch. We examined activity-dependent changes in evoked and miniature excitatory postsynaptic currents (eEPSCs and mEPSCs) at the calyx of Held synapse by breaking through the postsynaptic membrane at different time points following 2\u2009min of theta burst stimulation (TBS) to afferents in mouse brainstem slices. We found the decay time course of eEPSCs accelerated, but this change was not apparent until &gt;\u200930\u2009min after TBS. Histogram analyses of the decay time constants of mEPSCs for naive and tetanized synapses revealed two populations centered around \u03c4<jats:sub>fast<\/jats:sub>\u00a0\u2248\u20090.4 and 0.8\u2009ms, but the relative weight of the \u03c4<jats:sub>0.4<\/jats:sub> population over the \u03c4<jats:sub>0.8<\/jats:sub> population increased significantly only in tetanized synapses. Such changes are blocked by NMDAR or mGluR1\/5 antagonists or inhibitors of CaMKII, PKC and protein synthesis, and more importantly precluded in GluA4<jats:sup>\u2212\/\u2212<\/jats:sup> synapses, suggesting GluA4 is the substrate underlying the acceleration. Our results demonstrate a novel form of plasticity working through NMDAR and mGluR activation to trigger a gating switch of AMPARs with a temporally delayed onset of expression, ultimately enhancing the development of high-fidelity synaptic transmission.<\/jats:p>","DOI":"10.1186\/s13041-019-0536-2","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T10:02:32Z","timestamp":1579082552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Delayed expression of activity-dependent gating switch in synaptic AMPARs at a central synapse"],"prefix":"10.1186","volume":"13","author":[{"given":"Lee Stephen","family":"Lesperance","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Mei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5399-944X","authenticated-orcid":false,"given":"Lu-Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,15]]},"reference":[{"issue":"1","key":"536_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nrn2759","volume":"11","author":"AG Blankenship","year":"2010","unstructured":"Blankenship AG, Feller MB. 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All animal experiments were performed for this study in accordance with a protocol approved by the <i>Hospital for Sick Children Animal Care Committee.<\/i>","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not Applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6"}}