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In contrast, the magnitude of LTD induced by pharmacological activation of CA3\u2010CA1 group I metabotropic glutamate receptors (mGluRs) increases during aging. This study examined the signaling pathways involved in induction of LTD and the interaction between paired\u2010pulse low frequency stimulation\u2010induced synaptic\u2010LTD and group I mGluR selective agonist, (RS)\u20103,5\u2010dihydroxyphenylglycine (DHPG, 100 \u00b5M)\u2010induced DHPG\u2010LTD in hippocampal slices obtained from aged (22\u201324 months) male Fischer 344 rats. Prior induction of synaptic\u2010LTD did not affect induction of DHPG\u2010LTD; however, prior induction of the DHPG\u2010LTD occluded synaptic\u2010LTD suggesting that expression of DHPG\u2010LTD may incorporate synaptic\u2010LTD mechanisms. Application of individual antagonist for the group I mGluR (AIDA), the <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate receptor (NMDAR) (AP\u20105), or L\u2010type voltage\u2010dependent Ca<jats:sup>2+<\/jats:sup> channel (VDCC) (nifedipine) failed to block synaptic\u2010LTD and any two antagonists severely impaired synaptic\u2010LTD induction, indicating that activation of any two mechanisms is sufficient to induce synaptic\u2010LTD in aged animals. For DHPG\u2010LTD, AIDA blocked DHPG\u2010LTD and individually applied NMDAR or VDCC attenuated but did not block DHPG\u2010LTD, indicating that the magnitude of DHPG\u2010LTD depends on all three mechanisms. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/hipo.22240","type":"journal-article","created":{"date-parts":[[2014,1,4]],"date-time":"2014-01-04T10:26:46Z","timestamp":1388831206000},"page":"466-475","source":"Crossref","is-referenced-by-count":19,"title":["Interaction of DHPG\u2010LTD and synaptic\u2010LTD at senescent CA3\u2010CA1 hippocampal synapses"],"prefix":"10.1002","volume":"24","author":[{"given":"Ashok","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Neuroscience, McKnight Brain Institute University of Florida Gainesville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, McKnight Brain Institute 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