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The mechanisms by which Seipin mutations lead to motor neuropathy, lipodystrophy, and insulin resistance, and the role Seipin plays in central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) remain unknown. The goal of this study is to understand the functions of Seipin in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> using a loss\u2010of\u2010function approach, i.e. by knockdown (<jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content>) of Seipin gene expression. Excitatory post\u2010synaptic currents (<jats:styled-content style=\"fixed-case\">EPSC<\/jats:styled-content>s) were impaired in Seipin\u2010<jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content> neurons, while the inhibitory post\u2010synaptic currents (<jats:styled-content style=\"fixed-case\">IPSC<\/jats:styled-content>s) remained unaffected. Expression of a sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010resistant human Seipin rescued the impairment of <jats:styled-content style=\"fixed-case\">EPSC<\/jats:styled-content> produced by Seipin <jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content>. Furthermore, \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid (<jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content>)\u2010induced whole\u2010cell currents were significantly reduced in Seipin <jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content> neurons, which could be rescued by expression of a sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010resistant human Seipin. Fluorescent imaging and biochemical studies revealed reduced level of surface <jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content> receptors, while no obvious ultrastructural changes in the pre\u2010synapse were found. These data suggest that Seipin regulates excitatory synaptic function through a post\u2010synaptic mechanism.<\/jats:p>","DOI":"10.1111\/jnc.12099","type":"journal-article","created":{"date-parts":[[2012,11,22]],"date-time":"2012-11-22T15:45:41Z","timestamp":1353599141000},"page":"478-489","source":"Crossref","is-referenced-by-count":23,"title":["Seipin regulates excitatory synaptic transmission in cortical neurons"],"prefix":"10.1111","volume":"124","author":[{"given":"Shunhui","family":"Wei","sequence":"first","affiliation":[{"name":"Laboratory of Metabolic Medicine Singapore Bioimaging Consortium A*STAR Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie Li\u2010Ying","family":"Soh","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Medicine Singapore Bioimaging Consortium A*STAR 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