{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:04:56Z","timestamp":1783955096747,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25ek0109760"],"award-info":[{"award-number":["JP25ek0109760"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07423"],"award-info":[{"award-number":["20K07423"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K27566"],"award-info":[{"award-number":["23K27566"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K10508"],"award-info":[{"award-number":["24K10508"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants in the calcium\/calmodulin\u2010dependent protein kinase II B gene (\n                      <jats:italic>CAMK2B<\/jats:italic>\n                      ) have been associated with neurodevelopmental disorders, including epilepsy, yet the mechanisms underlying cortical dysfunction remain largely unclear. Building on our previous clinical report of a patient carrying the CaMKII\u03b2 P213L variant and our prior characterization of the corresponding mouse models, we investigated how P213L\u2010associated CaMKII\u03b2 insufficiency alters cortical network dynamics and susceptibility to pentylenetetrazol (PTZ)\u2013induced seizures in\u00a0vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed electroencephalographic recordings for CaMKII\u03b2 P213L knock\u2010in mice under baseline and pharmacological modulation. Susceptibility to seizure induction by the chemoconvulsant PTZ was assessed. Cortical CaMKII\u03b2 expression and Thr287 phosphorylation levels were quantified and compared to those in CaMKII\u03b2 knockout mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Heterozygous and homozygous knock\u2010in mice exhibited aberrant low\u2010gamma (20\u201350\u2009Hz) oscillations during resting state with behavioral immobility. These aberrant low\u2010gamma oscillations were sensitive to \u03b3\u2010aminobutyric acid (GABA)\u2010ergic modulation: pentylenetetrazol (PTZ) induced a downward shift in the gamma\u2010band peak frequency, whereas isoflurane, diazepam, and valproic acid suppressed the aberrant low\u2010gamma oscillations. PTZ administration increased seizure severity in both heterozygous and homozygous knock\u2010in mice, but lethality occurred only in homozygous mice. We quantified cortical CaMKII\u03b2 expression and Thr287 phosphorylation, both of which were reduced in knock\u2010in mice. Knockout mice recapitulated the aberrant low\u2010gamma oscillations and their pharmacological modulation observed in knock\u2010in mice, supporting the role of CaMKII\u03b2 insufficiency in driving the phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These findings suggest that CaMKII\u03b2 insufficiency disrupts cortical excitatory\u2013inhibitory balance, leading to the aberrant low\u2010gamma oscillations and increased seizure susceptibility. Our findings establish a mechanistic link between CaMKII\u03b2 deficiency and epilepsy\u2010related phenotypes in neurodevelopmental disorders. The P213L variant represents a loss\u2010of\u2010function variant with reduced CaMKII\u03b2 expression and phosphorylation, and provides a valuable model for investigating disease mechanisms and developing potential therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70250","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:45:31Z","timestamp":1776267931000},"page":"3766-3778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CaMKII\u03b2<\/scp>\n                    insufficiency disrupts cortical networks, producing aberrant low\u2010gamma oscillations and seizure susceptibility"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6832-5811","authenticated-orcid":false,"given":"Hiroki","family":"Mutoh","sequence":"first","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0304-9622","authenticated-orcid":false,"given":"Kazushi","family":"Aoto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Shizuoka Japan"},{"name":"Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7112-4834","authenticated-orcid":false,"given":"Atsuo","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Shizuoka Japan"},{"name":"Department of Neurophysiology Hamamatsu University School of Medicine  Hamamatsu Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0723-0960","authenticated-orcid":false,"given":"Hirotomo","family":"Saitsu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Shizuoka 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