{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:19:57Z","timestamp":1787998797497,"version":"build-2784847793"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H02777"],"award-info":[{"award-number":["18H02777"]}],"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":["25K11075"],"award-info":[{"award-number":["25K11075"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001951","name":"Angelman Syndrome Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001951","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of function of the maternally expressed\n                      <jats:italic>UBE3A<\/jats:italic>\n                      gene. Epilepsy and abnormal electroencephalographic (EEG) rhythms are key features, but their mechanisms and treatment remain unclear. Previous work showed that extrasynaptic \u03b3\u2010aminobutyric acid type A (GABA\n                      <jats:sub>A<\/jats:sub>\n                      ) receptor\u2010mediated tonic inhibition is reduced in cerebellar granule cells of AS model mice, contributing to motor deficits. Here, we evaluated tonic inhibition across brain regions and tested whether its dysregulation drives epilepsy, EEG abnormalities, and behavioral deficits in AS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Tonic inhibition was measured in principal neurons of the neocortex, hippocampus, and thalamus in maternal Ube3a knockout mice. We examined the effects of MP\u2010III\u2010022, an \u03b15\u2010containing GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptor\u2013selective positive allosteric modulator, and gaboxadol, a \u03b4\u2010containing GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptor agonist, on EEG, seizure threshold, and anxiety\u2010like behavior.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tonic inhibition was reduced in cortical layer 5 and hippocampal CA1 pyramidal neurons but preserved in thalamic relay neurons. This reduction correlated with elevated GAT1 expression in the cortex and hippocampus but not the thalamus. MP\u2010III\u2010022 reduced abnormal slow\u2010wave EEG activity, increased seizure thresholds, and improved anxiety\u2010like behavior. In contrast, gaboxadol enhanced slow\u2010wave activity and lowered seizure thresholds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Deficits in tonic inhibition in AS mice are region\u2010specific. These region\u2010dependent differences in tonic inhibition, rather than a global loss, likely underlie EEG abnormalities and heightened seizure susceptibility. \u03b15\u2010containing GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptors may offer a promising therapeutic target for adjunctive AS treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70307","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:04:53Z","timestamp":1780405493000},"page":"4348-4360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Region\u2010dependent differences in tonic inhibition underlie epileptic features in Angelman syndrome model mice"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3342-2210","authenticated-orcid":false,"given":"Miho","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Physiology Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3977-5340","authenticated-orcid":false,"given":"Takeru","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Miyoshi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Nakakubo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hokkaido University Graduate 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