Layer 5 myelination gates corticothalamic coincidence detection

Layer 5 myelination gates corticothalamic coincidence detection | 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 Layer 5 myelination gates corticothalamic coincidence detection Maarten Kole, Nora Jamann, Jorrit Montijn, Naomi Petersen, Roeland Lokhorst, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5459798/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Dec, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Myelin is essential for rapid saltatory propagation of action potentials (APs) to decrease the temporal delays between distant brain regions. Whether myelination plays a role in the long-range computational processing of disparate inputs is not well understood. Using a cell-type specific approach with retrograde AAV targeting in the layer 5 (L5) Cre-driver mouse line (Rbp4-Cre), we studied optogenetically evoked L5 pyramidal neuron responses and made in vivo juxtacellular recordings to determine the spike transfer to the posteromedial nucleus (POm) of the thalamus. Cuprizone-induced demyelination caused milliseconds of temporal delays and jitter of conduction times as well as failures in the high-frequency burst code. Computational models of the corticothalamic projection pathway revealed that grey matter myelin loss alone sufficed to account for the failure in burst propagation. Finally, pairing optically evoked spikes with whisker stimulation demonstrated that L5–POm myelination is critical for gating coincidence detection in the thalamus. Biological sciences/Neuroscience/Myelin biology and repair Biological sciences/Neuroscience/Neural circuits Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryinformationJamannetal.pdf Supplementary information MovieS1.mp4 Supplementary Movie 1 MovieS2.mp4 Supplementary Movie 2 Cite Share Download PDF Status: Published Journal Publication published 11 Dec, 2025 Read the published version in Nature Communications → 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. 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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-5459798","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":387861155,"identity":"853c5181-c95b-4d57-af38-e43fc1174b85","order_by":0,"name":"Maarten Kole","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYFACNgaGBww2IIoZIsBOjJYEhjQkLczEaTmMpJaQFt0GtsQHCRXn8/ikG5iNC2oOM5gT0mJ2gO2wQcKZ28VsMgeYk2ccO8xg2UxQC3ubRGLb7cQ2iQTmwzxstxkMDhOl5d85qJZ/RGlhOyaR2HAArCWZt40YLYfZkg0SjiUDtSQ2G/P2/echrOV4m+GDDzV2ifNnJB+W5vmWJmdwvIGAHkSQMoKV8hBQPwpGwSgYBaOAGAAABqA8z+MmLcgAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-3883-5682","institution":"Netherlands Institute for Neuroscience","correspondingAuthor":true,"prefix":"","firstName":"Maarten","middleName":"","lastName":"Kole","suffix":""},{"id":387861156,"identity":"75c06e62-86d0-4b55-8994-4bcc993e0289","order_by":1,"name":"Nora Jamann","email":"","orcid":"https://orcid.org/0000-0002-8875-4522","institution":"Netherlands Institute for Neuroscience","correspondingAuthor":false,"prefix":"","firstName":"Nora","middleName":"","lastName":"Jamann","suffix":""},{"id":387861157,"identity":"2c24f96d-1816-4eca-8346-90f632b523b0","order_by":2,"name":"Jorrit Montijn","email":"","orcid":"https://orcid.org/0000-0002-5621-090X","institution":"University of Amsterdam","correspondingAuthor":false,"prefix":"","firstName":"Jorrit","middleName":"","lastName":"Montijn","suffix":""},{"id":387861158,"identity":"762a2292-8a1a-4733-878f-4c94094e620e","order_by":3,"name":"Naomi Petersen","email":"","orcid":"","institution":"Netherlands Institute for Neurosciences","correspondingAuthor":false,"prefix":"","firstName":"Naomi","middleName":"","lastName":"Petersen","suffix":""},{"id":387861159,"identity":"f3260446-5d59-4c2c-bdf1-f1573938b4ec","order_by":4,"name":"Roeland Lokhorst","email":"","orcid":"","institution":"Netherlands Institute for Neuroscience","correspondingAuthor":false,"prefix":"","firstName":"Roeland","middleName":"","lastName":"Lokhorst","suffix":""},{"id":387861160,"identity":"f80a3b7b-6612-4a2c-a803-677a3f8933b1","order_by":5,"name":"Daan van den Burg","email":"","orcid":"","institution":"Netherlands Institute for Neuroscience","correspondingAuthor":false,"prefix":"","firstName":"Daan","middleName":"van den","lastName":"Burg","suffix":""},{"id":387861161,"identity":"0ac43822-d5e9-4c7f-9302-1c765a5d5323","order_by":6,"name":"Maayke Balemans","email":"","orcid":"","institution":"Netherlands Institute for Neuroscience","correspondingAuthor":false,"prefix":"","firstName":"Maayke","middleName":"","lastName":"Balemans","suffix":""},{"id":387861162,"identity":"e8002947-7816-483a-8abf-a00a4e6c53d1","order_by":7,"name":"Stan Driessens","email":"","orcid":"https://orcid.org/0009-0008-6742-2482","institution":"Netherlands Institute for Neuroscience","correspondingAuthor":false,"prefix":"","firstName":"Stan","middleName":"","lastName":"Driessens","suffix":""},{"id":387861163,"identity":"cb9eb82b-3484-46f0-8304-667300ab468b","order_by":8,"name":"J. 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