{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:57:35Z","timestamp":1790528255810,"version":"4.1.0"},"reference-count":72,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,2,7]]},"abstract":"<jats:p>\n                    Na\n                    <jats:sub>V<\/jats:sub>\n                    1.1 is the primary voltage-gated Na\n                    <jats:sup>+<\/jats:sup>\n                    channel in several classes of GABAergic interneurons, and its reduced activity leads to reduced excitability and decreased GABAergic tone. Here, we show that Na\n                    <jats:sub>V<\/jats:sub>\n                    1.1 channels are expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus. Mice carrying a heterozygous loss of function mutation in the\n                    <jats:italic>Scn1a<\/jats:italic>\n                    gene (\n                    <jats:italic>Scn1a<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    ), which encodes the pore-forming \u03b1-subunit of the Na\n                    <jats:sub>V<\/jats:sub>\n                    1.1 channel, have longer circadian period than WT mice and lack light-induced phase shifts. In contrast,\n                    <jats:italic>Scn1a<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice have exaggerated light-induced negative-masking behavior and normal electroretinogram, suggesting an intact retina light response.\n                    <jats:italic>Scn1a<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice show normal light induction of\n                    <jats:italic>c-Fos<\/jats:italic>\n                    and\n                    <jats:italic>mPer1<\/jats:italic>\n                    mRNA in ventral SCN but impaired gene expression responses in dorsal SCN. Electrical stimulation of the optic chiasm elicits reduced calcium transients and impaired ventro-dorsal communication in SCN neurons from\n                    <jats:italic>Scn1a<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice, and this communication is barely detectable in the homozygous gene KO (\n                    <jats:italic>Scn1a<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ). Enhancement of GABAergic transmission with tiagabine plus clonazepam partially rescues the effects of deletion of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.1 on circadian period and phase shifting. Our report demonstrates that a specific voltage-gated Na\n                    <jats:sup>+<\/jats:sup>\n                    channel and its associated impairment of SCN interneuronal communication lead to major deficits in the function of the master circadian pacemaker. Heterozygous loss of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.1 channels is the underlying cause for severe myoclonic epilepsy of infancy; the circadian deficits that we report may contribute to sleep disorders in severe myoclonic epilepsy of infancy patients.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1115729109","type":"journal-article","created":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T06:17:32Z","timestamp":1325830652000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["Na\n                    <sub>V<\/sub>\n                    1.1 channels are critical for intercellular communication in the suprachiasmatic nucleus and for normal circadian rhythms"],"prefix":"10.1073","volume":"109","author":[{"given":"Sung","family":"Han","sequence":"first","affiliation":[{"name":"Program in Neurobiology and Behavior and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank H.","family":"Yu","sequence":"additional","affiliation":[{"name":"Departments of bPharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Linton","sequence":"additional","affiliation":[{"name":"Program in Neurobiology and Behavior and"},{"name":"Biochemistry, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha M.","family":"Bosma","sequence":"additional","affiliation":[{"name":"Program in Neurobiology and Behavior and"},{"name":"Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Hurley","sequence":"additional","affiliation":[{"name":"Program in Neurobiology and Behavior and"},{"name":"Biochemistry, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Catterall","sequence":"additional","affiliation":[{"name":"Program in Neurobiology and Behavior and"},{"name":"Departments of bPharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horacio O.","family":"de la Iglesia","sequence":"additional","affiliation":[{"name":"Program in Neurobiology and Behavior and"},{"name":"Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,1,5]]},"reference":[{"key":"e_1_1_2_17_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2005.08.003"},{"key":"e_1_1_2_17_9_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135919"},{"key":"e_1_1_2_17_9_3_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2162-07.2007"},{"key":"e_1_1_2_17_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1754"},{"key":"e_1_1_2_17_9_5_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.187484"},{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1177"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2005.08.003"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90214-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.647"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135919"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3086"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1089287"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02890-6"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90120-A"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(94)00212-W"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80876-4"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.03.051"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1754"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2162-07.2007"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/320609"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00688.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000086379.71183.78"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.187484"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90238-9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-1-4615-1201-1_2","volume-title":"The Entrainment of Circadian Systems. 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