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Here, we studied its role for post\u2010natal cortical network function, which is poorly explored. To preclude early cortical migration defects caused by Reelin deficiency, we used a conditional Reelin knock\u2010out (Reln<jats:sup>cKO<\/jats:sup>) mouse, and induced Reelin deficiency post\u2010natally. Induced Reelin deficiency caused hyperexcitability of the neocortical network in vitro and ex vivo. Blocking Reelin binding to its receptors ApoER2 and VLDLR resulted in a similar effect. Hyperexcitability in Reln<jats:sup>cKO<\/jats:sup> organotypic slice cultures could be rescued by co\u2010culture with wild\u2010type organotypic slice cultures. Moreover, the GABA<jats:sub>B<\/jats:sub> receptor (GABA<jats:sub>B<\/jats:sub>R) agonist baclofen failed to activate and the antagonist CGP35348 failed to block GABA<jats:sub>B<\/jats:sub>Rs in Reln<jats:sup>cKO<\/jats:sup> mice. Immunolabeling of Reln<jats:sup>cKO<\/jats:sup> cortical slices revealed a reduction in GABA<jats:sub>B<\/jats:sub>R1 and GABA<jats:sub>B<\/jats:sub>R2 surface expression at the plasma membrane and western blot of Reln<jats:sup>cKO<\/jats:sup> cortical tissue revealed decreased phosphorylation of the GABA<jats:sub>B<\/jats:sub>R2 subunit at serine 892 and increased phosphorylation at serine 783, reflecting receptor deactivation and proteolysis. These data show a role of Reelin in controlling early network activity, by modulating GABA<jats:sub>B<\/jats:sub>R function.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14990-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Cover Image for this issue: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.15054\">https:\/\/doi.org\/10.1111\/jnc.15054<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14990","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T10:17:53Z","timestamp":1582280273000},"page":"589-603","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Reelin signaling modulates GABA<sub>B<\/sub> receptor function in the neocortex"],"prefix":"10.1111","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0198-389X","authenticated-orcid":false,"given":"Mohammad I. 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