Perturbation of cortical excitability in a conditional model of PCDH19 disorder

Perturbation of cortical excitability in a conditional model of PCDH19 disorder | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Perturbation of cortical excitability in a conditional model of PCDH19 disorder Didi Lamers, Silvia Landi, Roberta Mezzena, Laura Baroncelli, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1435434/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Jun, 2022 Read the published version in Cells → Version 1 posted You are reading this latest preprint version Abstract PCDH19 epilepsy (DEE9) is an X linked epilepsy syndrome associated to cognitive and behavioural disturbances. Unlike in most other X linked diseases, heterozygous females are affected while hemizygous males are spared. It has been proposed that DEE9 pathogenesis is related to disturbed cell-to-cell communication associated with mosaicism and consequential erroneous network wiring. However, the effects of mosaic PCDH19 expression on cortical network activity are unknown. We mimicked the pathology of DEE9 by introducing a patch of mosaic protein expression in the cortex of conditional PCDH19 knockout mice. LFP recordings demonstrate transient episodes of hyperexcitability and disturbed slow wave activity – a crucial component of NREM sleep. These alterations were also observed if the mosaic patch was introduced in adult mice, demonstrating that PCDH19 is not merely a developmental disease. Our results indicate that a focal mosaic mutation of PCDH19 disrupts network cortical computation and broaden our current understanding of DEE9. PCDH19 Epilepsy Girls Clustering Epilepsy Autism Spectrum Disorder Slow Wave Activity Excitation: Inhibition ratio NREM sleep Epilepsy Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 16 Jun, 2022 Read the published version in Cells → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1435434","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":90076328,"identity":"30db889f-6270-46df-a569-bfcd990b98b6","order_by":0,"name":"Didi Lamers","email":"","orcid":"https://orcid.org/0000-0001-5539-9870","institution":"Institute Nanoscience CNR and Scuola Normale Superiore Pisa","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Didi","middleName":"","lastName":"Lamers","suffix":""},{"id":90076329,"identity":"7ad8d345-79a0-4851-8742-46181c28dd8f","order_by":1,"name":"Silvia 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