{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T02:16:54Z","timestamp":1785377814011,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T00:00:00Z","timestamp":1610755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Many antiseizure drugs (ASDs) act on voltage\u2010dependent sodium channels, and the molecular basis of these effects is well established. In contrast, how ASDs act on the level of neuronal networks is much less understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, we determined the effects of eslicarbazepine (S\u2010Lic) on different types of inhibitory neurons, as well as inhibitory motifs. Experiments were performed in hippocampal slices from both sham\u2010control and chronically epileptic pilocarpine\u2010treated rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that S\u2010Lic causes an unexpected reduction of feed\u2010forward inhibition in the CA1 region at high concentrations (300\u00a0\u00b5M), but not at lower concentrations (100\u00a0\u00b5M). Concurrently, 300 but not 100\u00a0\u03bcM S\u2010Lic significantly reduced maximal firing rates in putative feed\u2010forward interneurons located in the CA1 stratum radiatum of sham\u2010control and epileptic animals. In contrast, feedback inhibition was not inhibited by S\u2010Lic. Instead, application of S\u2010Lic, in contrast to previous data for other drugs like carbamazepine (CBZ), resulted in a lasting potentiation of feedback inhibitory post\u2010synaptic currents (IPSCs) only in epileptic and not in sham\u2010control animals, which persisted after washout of S\u2010Lic. We hypothesized that this plasticity of inhibition might rely on anti\u2010Hebbian potentiation of excitatory feedback inputs onto oriens\u2010lacunosum moleculare (OLM) interneurons, which is dependent on Ca<jats:sup>2+<\/jats:sup>\u2010permeable \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid (AMPA) receptors. Indeed, we show that blocking Ca<jats:sup>2+<\/jats:sup>\u2010permeable AMPA receptors completely prevents upmodulation of feedback inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These results suggest that S\u2010Lic affects inhibitory circuits in the CA1 hippocampal region in unexpected ways. In addition, ASD actions may not be sufficiently explained by acute effects on their target channels, rather, it may be necessary to take plasticity of inhibitory circuits into account.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16808","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T12:30:05Z","timestamp":1610800205000},"page":"542-556","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Complex effects of eslicarbazepine on inhibitory micro networks in chronic experimental epilepsy"],"prefix":"10.1111","volume":"62","author":[{"given":"Sarah","family":"Schmidt","sequence":"first","affiliation":[{"name":"Medical Faculty Institute for Experimental Epileptology and Cognition Research University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Pothmann","sequence":"additional","affiliation":[{"name":"Medical Faculty Institute for Experimental Epileptology and Cognition Research University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"M\u00fcller\u2010Komorowska","sequence":"additional","affiliation":[{"name":"Medical Faculty Institute for Experimental Epileptology and Cognition Research University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thoralf","family":"Opitz","sequence":"additional","affiliation":[{"name":"Medical Faculty Institute for Experimental Epileptology and Cognition Research University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-5078","authenticated-orcid":false,"given":"Patr\u00edcio","family":"Soares da Silva","sequence":"additional","affiliation":[{"name":"BIAL \u2013Portela &amp; Ca. 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Mamede do Coronado Portugal"},{"name":"Unit of Pharmacology &amp; Therapeutics Department of Biomedicine Faculty of Medicine University of Porto Porto Portugal"},{"name":"MedInUP \u2013 Center for Drug Discovery and Innovative Medicines University of Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-998X","authenticated-orcid":false,"given":"Heinz","family":"Beck","sequence":"additional","affiliation":[{"name":"Medical Faculty Institute for Experimental Epileptology and Cognition Research University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2002.40501.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10473"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh682"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.43600.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2013.11.022"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.09.008"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14504"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu339"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0493-15.2015"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-09-03645.2002"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1621-05.2005"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2395-13.2014"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2594-18.2019"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02615"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137450"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0206-12.2012"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.09004.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.04.054"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2011.05.013"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03595.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.124"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1408710111"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-05-02697.1994"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.7.3631"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-21-09218.1999"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2396(20001215)38:4<489::AID-SYN15>3.0.CO;2-N"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000310"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-06-02168.1997"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16808","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.16808","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16808","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T18:27:50Z","timestamp":1693333670000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.16808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,16]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1111\/epi.16808"],"URL":"https:\/\/doi.org\/10.1111\/epi.16808","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,16]]},"assertion":[{"value":"2020-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}