{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:18:40Z","timestamp":1792790320033,"version":"4.5.0"},"posted":{"date-parts":[[2026,10,1]]},"group-title":"Neuroscience","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH National Institute of Neurological Disorders and Stroke","award":["T32 NS115724"],"award-info":[{"award-number":["T32 NS115724"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH National Institute of Neurological Disorders and Stroke","award":["1F31 NS14319501"],"award-info":[{"award-number":["1F31 NS14319501"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH National Institute of Neurological Disorders and Stroke","award":["K08 NS121464"],"award-info":[{"award-number":["K08 NS121464"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Michigan","award":["Kenneth Eisenberg Emerging Scholar award, Taubman Institute"],"award-info":[{"award-number":["Kenneth Eisenberg Emerging Scholar award, Taubman Institute"]}],"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Michigan","award":["Michigan Medicine Research Scouts Program"],"award-info":[{"award-number":["Michigan Medicine Research Scouts Program"]}],"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Michigan","award":["Mary & Peter Jessel Award"],"award-info":[{"award-number":["Mary & Peter Jessel Award"]}],"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Dravet Syndrome Foundation","award":["Postdoctoral Fellowship"],"award-info":[{"award-number":["Postdoctoral Fellowship"]}],"id":[{"id":"https:\/\/ror.org\/018hh3649","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Epilepsy Society","award":["Postdoctoral Fellowship"],"award-info":[{"award-number":["Postdoctoral Fellowship"]}],"id":[{"id":"https:\/\/ror.org\/01sx4nq39","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Veterans Affairs (VA) Ann Arbor Healthcare System","id":[{"id":"https:\/\/ror.org\/018txrr13","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Locus coeruleus (LC) neurons are the primary source of norepinephrine \/ noradrenaline (NE) released to most brain structures, including seizure-prone neocortical and limbic regions. LC-NE networks regulate numerous physiological processes, including arousal, attention, and memory. Previous evidence suggests that LC-NE neurons may be involved in epilepsy and that their activation may have therapeutic effects on seizures, but the endogenous activity of the LC-NE network during seizures remains largely unclear. We combined electrocorticography recordings and\n                  <jats:italic>in vivo<\/jats:italic>\n                  imaging to measure somatic activity of LC-NE neurons as well as downstream NE release during hyperthermia-induced seizures in a well-characterized pre-clinical model of Dravet Syndrome. We found that population LC-NE somatic activity was inhibited during seizures, whereas downstream NE release was dramatically elevated. To reconcile these discordant findings, we established that activation of downstream regions is capable of locally evoking NE release, in part via activation of glutamate receptors, consistent with the Glutamate Amplifies Noradrenergic Effects (GANE) model. Finally, we confirmed that ictal NE release occurred across additional downstream brain regions, epilepsy models, and seizure induction methods. Thus, disruption of NE signaling is likely a widespread ictal signature, with implications for impaired consciousness during and after seizures.\n                <\/jats:p>","DOI":"10.64898\/2026.09.25.754424","type":"posted-content","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:40:13Z","timestamp":1790880013000},"source":"Crossref","is-referenced-by-count":0,"title":["Seizures in a Dravet Syndrome mouse model inhibit the locus coeruleus but locally evoke supraphysiologic norepinephrine release"],"prefix":"10.64898","author":[{"given":"Meiling","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Michigan, Ann Arbor, MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiannos","family":"Demetriou","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Wayne State University, Detroit, MI 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