{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:29:40Z","timestamp":1789450180512,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,6,3]],"date-time":"2013-06-03T00:00:00Z","timestamp":1370217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hippocampus"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The family of toll\u2010like receptors (TLR) plays a major role in innate immunity due to their pathogen\u2010recognition abilities. TLR3 is a sensor for double\u2010stranded RNA, and regulates host\u2010defense responses to several viruses, via the production of type I interferons. Interferon\u2010\u03b2 (IFN\u03b2) is a primary product of TLR3 activation, and its transcription is elevated in the CNS response to the synthetic TLR3 ligand, polyinosinic\u2010polycytidylic acid (poly(I:C)). Peripheral infections, along with TLR\u2010induced inflammatory mediators, are known to have detrimental effects on brain function, exerting a negative impact on cognition and enhancing seizure susceptibility. In this study, we assessed hippocampal function in vitro, in response to systemic delivery of a TLR3 agonist. Unlike agonists of other TLRs, intraperitoneal injection of poly(I:C) did not adversely affect evoked short\u2010 and long\u2010term synaptic plasticity in mouse hippocampal slices. However, sustained and interictal\u2010like spontaneous activity was observed in CA1 pyramidal cells in response to poly(I:C) and this was associated with alterations in the expression of phosphorylated NR2B subunit\u2010containing NMDA receptors and an astrocyte\u2010specific glutamate\/aspartate transporter (GLAST) which impact on extracellular glutamate concentration and contribute to the genesis of epileptiform activity. We provide evidence for the production of IFN\u03b2 from microglia and astrocytes, and using mice deficient in the type I IFN receptor \u03b1 1 (IFNAR1), demonstrate that its subsequent activation is likely to underlie the TLR3\u2010mediated modulation of hippocampal excitability. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/hipo.22129","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T09:05:28Z","timestamp":1365066328000},"page":"696-707","source":"Crossref","is-referenced-by-count":75,"title":["Toll\u2010like receptor 3 activation modulates hippocampal network excitability, via glial production of interferon\u2010\u03b2"],"prefix":"10.1002","volume":"23","author":[{"given":"Derek A.","family":"Costello","sequence":"first","affiliation":[{"name":"Department of Physiology Trinity College Institute of Neuroscience Trinity College Dublin Dublin 2 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina A.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Physiology Trinity College Institute of Neuroscience Trinity College Dublin Dublin 2 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35099560"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22312"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-009-9297-5"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn271"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2009.06.004"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.255893"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12034"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(85)90091-6"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.280826"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6676-10.2011"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.02.002"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2006.12.007"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00935-08"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00650-6"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.01.033"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.04.004"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.04.024"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.07.025"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05171.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.65"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01224.2003"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110164"},{"key":"e_1_2_6_24_1","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1152\/jn.1996.75.5.1765","article-title":"Conditions for the induction of long\u2010term potentiation in layer II\/III horizontal connections of the rat motor cortex","volume":"75","author":"Hess G","year":"1996","journal-title":"J Neurophysiol"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.24.11284"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01488.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4320"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410240502"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1849"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1086\/591626"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:29:3:185"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20928"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-107"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04370.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2127"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(98)00048-5"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00380-7"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.08.012"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1987.57.3.869"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2005.06.009"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91607-T"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412170200"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-445X.1999.01892.x"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00701.x"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005807107"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2011.02.005"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.6.3916"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700004200"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806682105"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1146-08.2008"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061845"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1629"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20234"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6494-6"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.12.7540"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.03.007"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702553104"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.03.018"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-25-08692.2003"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1159\/000110455"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1140"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.04.002"},{"key":"e_1_2_6_63_1","first-page":"243","volume-title":"Epilepsia","author":"Wyneken U","year":"2003"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.5.2625"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139522"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.64.092501.114547"}],"container-title":["Hippocampus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhipo.22129","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hipo.22129","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T16:36:43Z","timestamp":1696351003000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hipo.22129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,3]]},"references-count":65,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1002\/hipo.22129"],"URL":"https:\/\/doi.org\/10.1002\/hipo.22129","archive":["Portico"],"relation":{},"ISSN":["1050-9631","1098-1063"],"issn-type":[{"value":"1050-9631","type":"print"},{"value":"1098-1063","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,3]]}}}