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Activity\u2010dependent long\u2010term depression (<jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content>) is a major form of synaptic plasticity related to memory and chronic pain. Previous studies of <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content> have mainly focused on the hippocampus, and no study in the <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content> has been reported. In this study, using a 64\u2010channel recording system, we show for the first time that repetitive low\u2010frequency stimulation (<jats:styled-content style=\"fixed-case\">LFS<\/jats:styled-content>) can elicit frequency\u2010dependent <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content> of glutamate receptor\u2010mediated excitatory synaptic transmission in both superficial and deep layers of the IC of adult mice. The induction of <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content> in the <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content> required activation of the <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate (<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>) receptor, metabotropic glutamate receptor (mGluR)5, and <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>\u2010type voltage\u2010gated calcium channel. Protein phosphatase 1\/2A and endocannabinoid signaling are also critical for the induction of <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content>. In contrast, inhibiting protein kinase <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>, protein kinase <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>, protein kinase M\u03b6 or calcium\/calmodulin\u2010dependent protein kinase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> did not affect <jats:styled-content style=\"fixed-case\">LFS<\/jats:styled-content>\u2010evoked <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content> in the <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>. Bath application of the group <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content> mGluR agonist (<jats:italic><jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content><\/jats:italic>)\u20103,5\u2010dihydroxyphenylglycine produced another form of <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content> in the <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>, which was <jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content> receptor\u2010independent and could not be occluded by <jats:styled-content style=\"fixed-case\">LFS<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content>. Our studies have characterised the basic mechanisms of <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content> in the <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content> at the network level, and suggest that two different forms of <jats:styled-content style=\"fixed-case\">LTD<\/jats:styled-content> may co\u2010exist in the same population of <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content> synapses.<\/jats:p>","DOI":"10.1111\/ejn.12330","type":"journal-article","created":{"date-parts":[[2013,8,12]],"date-time":"2013-08-12T04:22:25Z","timestamp":1376281345000},"page":"3128-3145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Long\u2010term depression of synaptic transmission in the adult mouse insular cortex <i>in vitro<\/i>"],"prefix":"10.1111","volume":"38","author":[{"given":"Ming\u2010Gang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Brain and Cognitive Sciences College of Natural Sciences Seoul National University Seoul Korea"},{"name":"Department of Physiology Faculty of Medicine University of Toronto 1 King's College Circle Toronto Ontario M5S 1A8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine University of Toronto 1 King's College Circle Toronto Ontario M5S 1A8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SukJae Joshua","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences College of Natural Sciences Seoul National University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham L.","family":"Collingridge","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences College of Natural Sciences Seoul National University Seoul Korea"},{"name":"Centre for Synaptic Plasticity School of Physiology and Pharmacology Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bong\u2010Kiun","family":"Kaang","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences College of Natural Sciences Seoul National University Seoul Korea"},{"name":"Department of Biological Sciences College of Natural Sciences National Creative Research Initiative Center for Memory Seoul National University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Gao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Fourth Military Medical University 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