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We have used a model of colonic inflammation induced by 2,4,6-trinitrobenzenesulfonic acid in Sprague Dawley rats to identify inflammation-induced changes in hippocampal synaptic transmission. Hippocampal slices obtained 4 d after the induction of inflammation revealed enhanced Schaffer collateral-induced excitatory field potentials in CA1 stratum radiatum. This was associated with larger-amplitude mEPSCs, but unchanged mEPSC frequencies and paired-pulse ratios, suggesting altered postsynaptic effects. Both AMPA- and NMDA-mediated synaptic currents were enhanced, and analysis of AMPA-mediated currents revealed increased contributions of GluR2-lacking receptors. In keeping with this, both transcripts and protein levels of the GluR2 subunit were reduced in hippocampus. Both long-term potentiation (LTP) and depression (LTD) were significantly reduced in hippocampal slices taken from inflamed animals. Chronic administration of the microglial\/macrophage activation inhibitor minocycline to the inflamed animals both lowered the level of the cytokine tumor necrosis factor \u03b1 in the hippocampus and completely abolished the effect of peripheral inflammation on the field potentials and synaptic plasticity (LTP and LTD). Our results reveal profound synaptic changes caused by a mirror microglia-mediated inflammatory response in hippocampus during peripheral organ inflammation. These synaptic changes may underlie the behavioral comorbidities seen in patients.<\/jats:p>","DOI":"10.1523\/jneurosci.4485-14.2015","type":"journal-article","created":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T16:21:08Z","timestamp":1427300468000},"page":"4942-4952","source":"Crossref","is-referenced-by-count":218,"title":["Microglia-Dependent Alteration of Glutamatergic Synaptic Transmission and Plasticity in the Hippocampus during Peripheral Inflammation"],"prefix":"10.1523","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2291-7405","authenticated-orcid":false,"given":"Kiarash","family":"Riazi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Galic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7069-486X","authenticated-orcid":false,"given":"Amanda C.","family":"Kentner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin Y.","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Sharkey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0984-7665","authenticated-orcid":false,"given":"Quentin J.","family":"Pittman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2015,3,25]]},"reference":[{"key":"2023041304161372000_35.12.4942.1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(200002)35:2<151::AID-SYN8>3.0.CO;2-P"},{"key":"2023041304161372000_35.12.4942.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067859"},{"key":"2023041304161372000_35.12.4942.3","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90959-Q"},{"key":"2023041304161372000_35.12.4942.4","doi-asserted-by":"publisher","DOI":"10.1038\/nn1682"},{"key":"2023041304161372000_35.12.4942.5","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2014_309"},{"key":"2023041304161372000_35.12.4942.6","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90049-7"},{"key":"2023041304161372000_35.12.4942.7","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.99"},{"key":"2023041304161372000_35.12.4942.8","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.199"},{"key":"2023041304161372000_35.12.4942.9","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-1-25"},{"key":"2023041304161372000_35.12.4942.10","doi-asserted-by":"publisher","DOI":"10.1101\/lm.030775.113"},{"key":"2023041304161372000_35.12.4942.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.01.019"},{"key":"2023041304161372000_35.12.4942.12","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1556"},{"key":"2023041304161372000_35.12.4942.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.01.028"},{"key":"2023041304161372000_35.12.4942.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.06.006"},{"key":"2023041304161372000_35.12.4942.15","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2297"},{"key":"2023041304161372000_35.12.4942.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.12.009"},{"key":"2023041304161372000_35.12.4942.17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00184.2011"},{"key":"2023041304161372000_35.12.4942.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2013.10.009"},{"key":"2023041304161372000_35.12.4942.19","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1329-13.2013"},{"key":"2023041304161372000_35.12.4942.20","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.187229"},{"key":"2023041304161372000_35.12.4942.21","first-page":"436813","article-title":"Parkinson's disease and systemic inflammation","volume":"2011","author":"Ferrari","year":"2011","journal-title":"Parkinsons Dis"},{"key":"2023041304161372000_35.12.4942.22","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0022-3565(24)37138-1","article-title":"Ro 25-6981, a highly potent and selective blocker of N-methyl-d-aspartate receptors containing the NR2B subunit. 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