Postnatal reduction of eIF4E overexpression in D1-SPNs ameliorates KCNQ channel dysfunction, hyperexcitability and ASD-like behaviours.

Postnatal reduction of eIF4E overexpression in D1-SPNs ameliorates KCNQ channel dysfunction, hyperexcitability and ASD-like behaviours. | 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 Research Article Postnatal reduction of eIF4E overexpression in D1-SPNs ameliorates KCNQ channel dysfunction, hyperexcitability and ASD-like behaviours. Alina Aaltonen, Ayu Tamaki, Andrés Peris Ramón, Anders Borgkvist, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7400115/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Feb, 2026 Read the published version in Cellular and Molecular Life Sciences → Version 1 posted 5 You are reading this latest preprint version Abstract An imbalance between the direct and indirect pathways of the striatum has been linked to the pathophysiology of autism spectrum disorder (ASD), manifesting as repetitive behaviours and hyperactivity. We have investigated cell-specific dysfunctions in spiny projection neurons (SPNs) in a mouse model of ASD characterised by elevated expression of the eukaryotic initiation factor 4E (eIF4E), a key regulator of cap-dependent translation. eIF4E-TG mice, which exhibit ASD-like motor behaviours, were examined using a combination of fibre photometry, electrophysiology, conditional gene silencing, and behavioural assays. Direct pathway SPNs showed elevated activity during exploratory behaviour, along with hyperexcitability and reduced KCNQ potassium channel function in striatal slices. Conditional reduction of eIF4E in direct pathway SPNs of adult mice restored KCNQ channel function, normalised excitability, and ameliorated repetitive and hyperactive behaviours. These findings provide novel evidence that eIF4E-dependent translation regulates potassium channel function in direct pathway SPNs, and that postnatal targeting of eIF4E may be sufficient to treat motor dysfunction relevant to ASD. Full Text Supplementary Files Supplementalinformation250818.pdf Cite Share Download PDF Status: Published Journal Publication published 18 Feb, 2026 Read the published version in Cellular and Molecular Life Sciences → Version 1 posted Editorial decision: Major Revision 15 Oct, 2025 Reviewers agreed at journal 03 Sep, 2025 Reviewers invited by journal 28 Aug, 2025 Editor assigned by journal 22 Aug, 2025 First submitted to journal 20 Aug, 2025 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. 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