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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,16]]},"abstract":"<jats:p>\n                    Epilepsy is a common neurological disorder, which has been linked to mutations or deletions of RNA binding protein, fox-1 homolog (\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    ) 3 (\n                    <jats:italic>RBFOX3<\/jats:italic>\n                    )\/\n                    <jats:italic>NeuN<\/jats:italic>\n                    , a neuronal splicing regulator. However, the mechanism of seizure mediation by RBFOX3 remains unknown. Here, we show that mice with deletion of\n                    <jats:italic>Rbfox3<\/jats:italic>\n                    in gamma-aminobutyric acid (GABA) ergic neurons exhibit spontaneous seizures and high premature mortality due to increased presynaptic release, postsynaptic potential, neuronal excitability, and synaptic transmission in hippocampal dentate gyrus granule cells (DGGCs). Attenuating early excitatory gamma-aminobutyric acid (GABA) action by administering bumetanide, an inhibitor of early GABA depolarization, rescued premature mortality.\n                    <jats:italic>Rbfox3<\/jats:italic>\n                    deletion reduced hippocampal expression of vesicle-associated membrane protein 1 (VAMP1), a GABAergic neuron-specific presynaptic protein. Postnatal restoration of VAMP1 rescued premature mortality and neuronal excitability in DGGCs. Furthermore,\n                    <jats:italic>Rbfox3<\/jats:italic>\n                    deletion in GABAergic neurons showed fewer neuropeptide Y (NPY)\u2013expressing GABAergic neurons. In addition, deletion of\n                    <jats:italic>Rbfox3<\/jats:italic>\n                    in NPY-expressing GABAergic neurons lowered intrinsic excitability and increased seizure susceptibility. Our results establish RBFOX3 as a critical regulator and possible treatment path for epilepsy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2203632119","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T13:47:49Z","timestamp":1660225669000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":19,"title":["Neuronal splicing regulator RBFOX3 mediates seizures via regulating\n                    <i>Vamp1<\/i>\n                    expression preferentially in NPY-expressing GABAergic neurons"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-3650","authenticated-orcid":false,"given":"De-Fong","family":"Huang","sequence":"first","affiliation":[{"name":"Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Yu","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"},{"name":"Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0685-0535","authenticated-orcid":false,"given":"Ming-Yi","family":"Chou","sequence":"additional","affiliation":[{"name":"Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Yin","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Cao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsuan","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0823-9388","authenticated-orcid":false,"given":"Rui-Ni","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chang","family":"Lien","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Shuian","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-305X","authenticated-orcid":false,"given":"Hsiang-Po","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan Shur-Fen","family":"Gau","sequence":"additional","affiliation":[{"name":"Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"},{"name":"Department of Psychiatry, National Taiwan University Hospital and College of Medicine, 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