{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T03:12:17Z","timestamp":1776049937215,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2019,8,24]],"date-time":"2019-08-24T00:00:00Z","timestamp":1566604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 2016-18925"],"award-info":[{"award-number":["IG 2016-18925"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007368","name":"Fondazione Pisa","doi-asserted-by":"publisher","award":["NanoBioMarker 2016"],"award-info":[{"award-number":["NanoBioMarker 2016"]}],"id":[{"id":"10.13039\/100007368","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The correct morphofunctional shaping of the cerebral cortex requires a continuous interaction between intrinsic (genes\/molecules expressed within the tissue) and extrinsic (e.g., neural activity) factors at all developmental stages. Forkhead Box G1 (FOXG1) is an evolutionarily conserved transcription factor, essential for the cerebral cortex patterning and layering. FOXG1-related disorders, including the congenital form of Rett syndrome, can be caused by deletions, intragenic mutations or duplications. These genetic alterations are associated with a complex phenotypic spectrum, spanning from intellectual disability, microcephaly, to autistic features, and epilepsy. We investigated the functional correlates of dysregulated gene expression by performing electrophysiological assays on FoxG1+\/\u2212 mice. Local Field Potential (LFP) recordings on freely moving animals detected cortical hyperexcitability. On the other hand, patch-clamp recordings showed a downregulation of spontaneous glutamatergic transmission. These findings were accompanied by overactivation of Akt\/S6 signaling. Furthermore, the expression of vesicular glutamate transporter 2 (vGluT2) was increased, whereas the level of the potassium\/chloride cotransporter KCC2 was reduced, thus indicating a higher excitation\/inhibition ratio. Our findings provide evidence that altered expression of a key gene for cortical development can result in specific alterations in neural circuit function at the macro- and micro-scale, along with dysregulated intracellular signaling and expression of proteins controlling circuit excitability.<\/jats:p>","DOI":"10.3390\/ijms20174127","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T04:38:23Z","timestamp":1566794303000},"page":"4127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Cortical Seizures in FoxG1+\/\u2212 Mice are Accompanied by Akt\/S6 Overactivation, Excitation\/Inhibition Imbalance and Impaired Synaptic Transmission"],"prefix":"10.3390","volume":"20","author":[{"given":"Giovanna","family":"Testa","sequence":"first","affiliation":[{"name":"Laboratory of Biology \u201cBio@SNS\u201d, Scuola Normale Superiore, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Olimpico","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Italian National Research Council (IN-CNR), 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Pancrazi","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Italian National Research Council (IN-CNR), 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9812-579X","authenticated-orcid":false,"given":"Ugo","family":"Borello","sequence":"additional","affiliation":[{"name":"Unit of Cell and Developmental Biology, Department of Biology, University of Pisa, 56123 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonino","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Laboratory of Biology \u201cBio@SNS\u201d, Scuola Normale Superiore, 56126 Pisa, Italy"},{"name":"European Brain Research Institute \u201cRita Levi-Montalcini\u201d (EBRI), 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-6378","authenticated-orcid":false,"given":"Matteo","family":"Caleo","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Italian National Research Council (IN-CNR), 56124 Pisa, Italy"},{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Costa","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Italian National Research Council (IN-CNR), 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Mainardi","sequence":"additional","affiliation":[{"name":"Laboratory of Biology \u201cBio@SNS\u201d, Scuola Normale Superiore, 56126 Pisa, Italy"},{"name":"Institute of Neuroscience, Italian National Research Council (IN-CNR), 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.tig.2014.12.004","article-title":"From trans to cis: Transcriptional regulatory networks in neocortical development","volume":"31","author":"Shibata","year":"2015","journal-title":"Trends Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.neuron.2011.12.030","article-title":"A radial glia-specific role of RhoA in double cortex formation","volume":"73","author":"Cappello","year":"2012","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.nbd.2015.08.003","article-title":"Neuronal migration disorders: Focus on the cytoskeleton and epilepsy","volume":"92","author":"Stouffer","year":"2016","journal-title":"Neurobiol. 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