{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:46:53Z","timestamp":1791121613019,"version":"4.1.0"},"reference-count":38,"publisher":"Society for Neuroscience","issue":"4","license":[{"start":{"date-parts":[[2006,7,25]],"date-time":"2006-07-25T00:00:00Z","timestamp":1153785600000},"content-version":"vor","delay-in-days":181,"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":[[2006,1,25]]},"abstract":"<jats:p>Synaptic plasticity of NMDA receptor (NMDAR)-mediated transmission was investigated in the rat dentate gyrus<jats:italic>in vitro<\/jats:italic>. Isolated NMDAR EPSCs were recorded from granule cells of the dentate gyrus in response to stimulation of the medial perforant path. Long-term potentiation (LTP) or long-term depression (LTD) of NMDAR EPSCs was observed in response to brief high-frequency stimulation (HFS), with the direction and extent of plasticity dependent on the concentration and type (EGTA vs BAPTA) of the intracellular Ca<jats:sup>2+<\/jats:sup>buffer. LTD was induced in higher concentrations of EGTA and BAPTA than LTP, and BAPTA was \u223c100-fold more potent than EGTA. Although LTD was induced in a high concentration of EGTA (10 m<jats:sc>m<\/jats:sc>), a high concentration of BAPTA (10 m<jats:sc>m<\/jats:sc>) blocked both LTP and LTD. LTP of AMPA receptor (AMPAR)-EPSCs exhibited a lower dependency on Ca<jats:sup>2+<\/jats:sup>buffering than LTP of NMDAR EPSCs, because LTP of AMPAR EPSCs was induced by HFS in high EGTA (10 m<jats:sc>m<\/jats:sc>). We also identified a role for metabotropic glutamate receptor 5 (mGluR5) in NMDAR plasticity. HFS LTD was blocked by the group I\/II mGluR antagonist<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"LY341495\" ext-link-type=\"gen\" xlink:type=\"simple\">LY341495<\/jats:ext-link>((2<jats:italic>S<\/jats:italic>)-2-amino-2-[(1<jats:italic>S<\/jats:italic>, 2<jats:italic>S<\/jats:italic>)-2-carboxycycloprop-1-yl]-3(xanth-9-yl)propanoic acid) and by the mGluR5-selective antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). Similarly, low-frequency stimulation-induced LTD of NMDAR EPSCs was also blocked by MPEP. These findings suggest that the direction of plasticity of NMDARs is determined by the intracellular free Ca<jats:sup>2+<\/jats:sup>concentration and is dependent on activation of mGluR5.<\/jats:p>","DOI":"10.1523\/jneurosci.2753-05.2006","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T20:28:04Z","timestamp":1138220884000},"page":"1128-1132","source":"Crossref","is-referenced-by-count":106,"title":["Long-Term Depression of NMDA Receptor-Mediated Synaptic Transmission Is Dependent on Activation of Metabotropic Glutamate Receptors and Is Altered to Long-Term Potentiation by Low Intracellular Calcium Buffering"],"prefix":"10.1523","volume":"26","author":[{"given":"Sarah C.","family":"Harney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Anwyl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2006,1,25]]},"reference":[{"key":"2023041303163199000_26.4.1128.1","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1523\/JNEUROSCI.11-06-01496.1991","volume":"11","year":"(1991)","journal-title":"J Neurosci"},{"key":"2023041303163199000_26.4.1128.2","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1152\/jn.1995.74.6.2349","volume":"74","year":"(1995)","journal-title":"J Neurophysiol"},{"key":"2023041303163199000_26.4.1128.3","doi-asserted-by":"crossref","unstructured":"Anwyl R (2006) Induction and expression mechanisms of postsynaptic NMDA receptor-independent homosynaptic long-term depression. 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