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While the pathways underlying seizure rhythmicity remain poorly understood, it seems likely that a contribution from the biological clock is involved. A better understanding of any such contribution may translate to better treatments. Here, the influence of the 24-h circadian rhythm on seizure activity in\n                    <jats:italic toggle=\"yes\">Drosophila melanogaster<\/jats:italic>\n                    is investigated. Seizure-susceptible bang-sensitive mutants (\n                    <jats:italic toggle=\"yes\">julius seizure<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">\n                      paralytic\n                      <jats:sup>bangsenseless1<\/jats:sup>\n                    <\/jats:italic>\n                    ) were subjected to mechanically induced seizure at 6 different zeitgeber points. A clear sex-dependent phenotype was observed, with seizure severity showing a greater time-of-day effect in females than males. The temporal pattern of seizure recovery time was bimodal, exhibiting both a morning and an evening peak. Rearing flies in constant light (LL), which renders the molecular clock dysfunctional, abolished the seizure rhythm. Conversely, female seizure mutants reared in constant darkness (DD), allowing free running of the circadian clock, continued to exhibit a bimodal rhythm of seizure severity. Moreover, seizure mutant females lacking a functional clock (\n                    <jats:italic toggle=\"yes\">\n                      period\n                      <jats:sup>0<\/jats:sup>\n                    <\/jats:italic>\n                    ) did not show rhythmicity of seizure severity. These findings support a role for the biological clock in seizure activity, at least in female\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    . Finally, seizure mutant females showed normal PERIOD clock protein intensity oscillations in clock neurons, supporting the hypothesis that seizure rhythmicity requires a functional circadian clock. Thus, this study validates\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    as a potential model for the identifying the mechanisms modulating seizure rhythmicity, with the potential to aid future treatment of epilepsy.\n                  <\/jats:p>","DOI":"10.1177\/07487304261428337","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:23:42Z","timestamp":1775798622000},"page":"400-415","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Circadian Rhythms Time Seizure Severity in\n                    <i>Drosophila<\/i>"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8665-8595","authenticated-orcid":false,"given":"Mariam","family":"Huertas-Radi","sequence":"first","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK"},{"name":"Institute of Neuro- and Behavioural Biology, Multiscale Imaging Centre, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7442-324X","authenticated-orcid":false,"given":"Adam A.","family":"Bradlaugh","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-4376","authenticated-orcid":false,"given":"Richard A.","family":"Baines","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"crossref","unstructured":"Akpoghiran O Strich AK Koh K (2024) Effects of sex mating status and genetic background on circadian behavior in Drosophila. bioRxiv. https:\/\/doi.org\/10.1101\/2024.11.22.624853.","DOI":"10.1101\/2024.11.22.624853"},{"key":"e_1_3_4_3_1","doi-asserted-by":"crossref","unstructured":"Bermudez S Dean DM Alkin V Wang Z Pham H Kondo E Amini A Deitcher DL (2023) A complex containing the Na+\/K+ ATPase regulates epileptogenesis in Drosophila melanogaster. bioRxiv. https:\/\/doi.org\/10.1101\/2023.09.22.559031.","DOI":"10.1101\/2023.09.22.559031"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212531"},{"key":"e_1_3_4_5_1","article-title":"Assaying locomotor activity to study circadian rhythms and sleep parameters in drosophila","volume":"43","author":"Chiu JC","year":"2010","unstructured":"Chiu JC, Low KH, Pike DH, Yildirim E, Edery I (2010) Assaying locomotor activity to study circadian rhythms and sleep parameters in drosophila. 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