{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:04:14Z","timestamp":1782281054111,"version":"3.54.5"},"posted":{"date-parts":[[2024,8,27]]},"group-title":"Neuroscience","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Animal models of epilepsy are critical in drug development and therapeutic testing, but dominant methods for pharmaceutical evaluation face a tradeoff between higher throughput and etiological relevance. For example, in temporal lobe epilepsy, a type of epilepsy where seizures originate from limbic structures like the hippocampus, the main screening models are either based on acutely induced seizures in wild type, na\u00efve animals or spontaneous seizures in chronically epileptic animals. Both types have their disadvantages \u2013 the acute convulsant or kindling induced seizures do not account for the myriad neuropathological changes in the diseased, epileptic brains, and spontaneous behavioral seizures are sparse in the chronically epileptic models, making it time-intensive to sufficiently power experiments. In this study, we took a mechanistic approach to precipitate seizures \u201con demand\u201d in chronically epileptic mice. We briefly synchronized principal cells in the CA1 region of the diseased hippocampus to reliably induce stereotyped on-demand behavioral seizures. These induced seizures resembled naturally occurring spontaneous seizures in the epileptic animals and could be stopped by commonly prescribed anti-seizure medications such as levetiracetam and diazepam. Furthermore, we showed that seizures induced in chronically epileptic animals differed from those in na\u00efve animals, highlighting the importance of evaluating therapeutics in the diseased circuit. Taken together, we envision our model to advance the speed at which both pharmacological and closed loop interventions for temporal lobe epilepsy are evaluated.<\/jats:p>","DOI":"10.1101\/2024.08.26.609726","type":"posted-content","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T15:50:11Z","timestamp":1724773811000},"source":"Crossref","is-referenced-by-count":0,"title":["On-Demand Seizures Facilitate Rapid Screening of Therapeutics for Epilepsy"],"prefix":"10.64898","author":[{"given":"Yuzhang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Litt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Vitale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3033-2412","authenticated-orcid":false,"given":"Hajime","family":"Takano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025043020055017000_2024.08.26.609726v3.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01048-6"},{"key":"2025043020055017000_2024.08.26.609726v3.2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003509"},{"key":"2025043020055017000_2024.08.26.609726v3.3","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14596"},{"key":"2025043020055017000_2024.08.26.609726v3.4","first-page":"2605","article-title":"Managing drug-resistant epilepsy: Challenges and solutionsNeuropsychiatr","volume":"12","year":"2016","journal-title":"Dis. Treat"},{"key":"2025043020055017000_2024.08.26.609726v3.5","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011839"},{"key":"2025043020055017000_2024.08.26.609726v3.6","doi-asserted-by":"publisher","DOI":"10.1124\/pr.120.019539"},{"key":"2025043020055017000_2024.08.26.609726v3.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00410-5"},{"key":"2025043020055017000_2024.08.26.609726v3.8","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROPHARM.2019.107811"},{"key":"2025043020055017000_2024.08.26.609726v3.9","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS12091233"},{"key":"2025043020055017000_2024.08.26.609726v3.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2016.12.074"},{"key":"2025043020055017000_2024.08.26.609726v3.11","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12458"},{"key":"2025043020055017000_2024.08.26.609726v3.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00421-1"},{"key":"2025043020055017000_2024.08.26.609726v3.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-19-08312.1999"},{"key":"2025043020055017000_2024.08.26.609726v3.14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-14-05401.2000"},{"key":"2025043020055017000_2024.08.26.609726v3.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(02)00072-4"},{"key":"2025043020055017000_2024.08.26.609726v3.16","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S50371"},{"key":"2025043020055017000_2024.08.26.609726v3.17","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0337-20.2021"},{"key":"2025043020055017000_2024.08.26.609726v3.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.08.020"},{"key":"2025043020055017000_2024.08.26.609726v3.19","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2239-3"},{"key":"2025043020055017000_2024.08.26.609726v3.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(96)00055-1"},{"key":"2025043020055017000_2024.08.26.609726v3.21","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2275-z"},{"key":"2025043020055017000_2024.08.26.609726v3.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131080"},{"key":"2025043020055017000_2024.08.26.609726v3.23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0980-08.2009"},{"key":"2025043020055017000_2024.08.26.609726v3.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.09.015"},{"key":"2025043020055017000_2024.08.26.609726v3.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.11.015"},{"key":"2025043020055017000_2024.08.26.609726v3.26","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.4.2231"},{"key":"2025043020055017000_2024.08.26.609726v3.27","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0441-21.2022"},{"key":"2025043020055017000_2024.08.26.609726v3.28","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00184.2010"},{"key":"2025043020055017000_2024.08.26.609726v3.29","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990614)408:4<449::AID-CNE1>3.0.CO;2-R"},{"key":"2025043020055017000_2024.08.26.609726v3.30","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52760"},{"key":"2025043020055017000_2024.08.26.609726v3.31","doi-asserted-by":"publisher","DOI":"10.2174\/157015911795596540"},{"key":"2025043020055017000_2024.08.26.609726v3.32","doi-asserted-by":"publisher","DOI":"10.1113\/JP270056"},{"key":"2025043020055017000_2024.08.26.609726v3.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.11.025"},{"key":"2025043020055017000_2024.08.26.609726v3.34","doi-asserted-by":"publisher","DOI":"10.3390\/s21113786"},{"key":"2025043020055017000_2024.08.26.609726v3.35","doi-asserted-by":"crossref","unstructured":"R. D\u2019Ambrosio , J. W. Miller , What Is an Epileptic Seizure? Unifying Definitions in Clinical Practice and Animal Research to Develop Novel Treatments. Epilepsy Curr. 10, 61 (2010).","DOI":"10.1111\/j.1535-7511.2010.01358.x"},{"key":"2025043020055017000_2024.08.26.609726v3.36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25010660"},{"key":"2025043020055017000_2024.08.26.609726v3.37","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3482"},{"key":"2025043020055017000_2024.08.26.609726v3.38","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00298"},{"key":"2025043020055017000_2024.08.26.609726v3.39","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2016.00119"},{"key":"2025043020055017000_2024.08.26.609726v3.40","doi-asserted-by":"publisher","DOI":"10.5698\/1535-7597-16.1.48"},{"key":"2025043020055017000_2024.08.26.609726v3.41","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16901"},{"key":"2025043020055017000_2024.08.26.609726v3.42","doi-asserted-by":"publisher","DOI":"10.3390\/ph15040475"},{"key":"2025043020055017000_2024.08.26.609726v3.43","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00031"},{"key":"2025043020055017000_2024.08.26.609726v3.44","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00131.2004"},{"key":"2025043020055017000_2024.08.26.609726v3.45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb01259.x"},{"key":"2025043020055017000_2024.08.26.609726v3.46","doi-asserted-by":"crossref","unstructured":"E. R. G. Sanabria , H. Su , Y. Yaari , Initiation of network bursts by Ca2+-dependent intrinsic bursting in the rat pilocarpine model of temporal lobe epilepsy. J. Physiol. 532, 205 (2001).","DOI":"10.1111\/j.1469-7793.2001.0205g.x"},{"key":"2025043020055017000_2024.08.26.609726v3.47","first-page":"1","article-title":"The temporoammonic input to the hippocampal CA1 region displays distinctly different synaptic plasticity compared to the Schaffer collateral input in vivo: Significance for synaptic information processing","volume":"5","year":"2013","journal-title":"Front. Synaptic Neurosci"},{"key":"2025043020055017000_2024.08.26.609726v3.48","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2354-06.2006"},{"key":"2025043020055017000_2024.08.26.609726v3.49","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.8.1403"},{"key":"2025043020055017000_2024.08.26.609726v3.50","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)37251-9"},{"key":"2025043020055017000_2024.08.26.609726v3.51","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90768-D"},{"key":"2025043020055017000_2024.08.26.609726v3.52","doi-asserted-by":"publisher","DOI":"10.1007\/s12021-019-09446-7"},{"key":"2025043020055017000_2024.08.26.609726v3.53","doi-asserted-by":"publisher","DOI":"10.1038\/74159"},{"key":"2025043020055017000_2024.08.26.609726v3.54","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02924-9"},{"key":"2025043020055017000_2024.08.26.609726v3.55","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01040.2014"},{"key":"2025043020055017000_2024.08.26.609726v3.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41711-x"},{"key":"2025043020055017000_2024.08.26.609726v3.57","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14680"},{"key":"2025043020055017000_2024.08.26.609726v3.58","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12523"},{"key":"2025043020055017000_2024.08.26.609726v3.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2016.11.035"},{"key":"2025043020055017000_2024.08.26.609726v3.60","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz209"},{"key":"2025043020055017000_2024.08.26.609726v3.61","doi-asserted-by":"publisher","DOI":"10.1016\/00134694(72)90177-0"},{"key":"2025043020055017000_2024.08.26.609726v3.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.10.001"},{"key":"2025043020055017000_2024.08.26.609726v3.63","first-page":"1707","article-title":"Line length: An efficient feature for seizure onset detection","volume":"2","year":"2001","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol"},{"key":"2025043020055017000_2024.08.26.609726v3.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.aci.2015.01.001"},{"key":"2025043020055017000_2024.08.26.609726v3.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81132-8"},{"key":"2025043020055017000_2024.08.26.609726v3.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.artmed.2017.12.004"},{"key":"2025043020055017000_2024.08.26.609726v3.67","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001656"},{"key":"2025043020055017000_2024.08.26.609726v3.68","first-page":"1","article-title":"A Feature Extraction Method for Seizure Detection Based on Multi-Site Synchronous Changes and Edge Detection Algorithm","volume":"13","year":"2023","journal-title":"Brain Sci"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.08.26.609726","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:13:52Z","timestamp":1782278032000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.08.26.609726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,27]]},"references-count":68,"URL":"https:\/\/doi.org\/10.1101\/2024.08.26.609726","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.7554\/eLife.101859","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.101859.3","asserted-by":"object"}],"has-version":[{"id-type":"doi","id":"10.7554\/eLife.101859.1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.101859.2","asserted-by":"object"}]},"subject":[],"published":{"date-parts":[[2024,8,27]]},"subtype":"preprint"}}