Diffusion-mediated nonlinear coupling drives ephaptic synchronization and Cross-Frequency Coordination

Diffusion-mediated nonlinear coupling drives ephaptic synchronization and Cross-Frequency Coordination | 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 Diffusion-mediated nonlinear coupling drives ephaptic synchronization and Cross-Frequency Coordination Seido Nagano This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9118948/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Action-potential synchronization mediated by ephaptic interactions poses a fundamental biophysical challenge: extracellular ionic fluctuations from a single spike are generally considered too small to significantly influence neighboring neurons. However, experimental evidence demonstrates that transient changes in extracellular ion concentrations can modulate adjacent cell excitability and promote mutual synchronization. To reconcile this discrepancy, we propose that extracellular ion diffusion functions as a nonlinear coupling term between excitable cells possessing limit-cycle dynamics. We demonstrate that even minute extracellular perturbations are amplified by the intrinsic nonlinear dynamics of the membrane potential governing voltage-gated ion channels. Within this framework, ephaptic synchronization enhances the reliability of neuronal firing and supports robust signal propagation. Furthermore, these interactions facilitate cross-frequency synchronization, where neurons with distinct intrinsic firing rates achieve coordination while maintaining stable phase offsets. Beyond temporal alignment, synchronized firing increases action-potential amplitude, potentially strengthening synaptic efficacy. At the network level, global synchronization induced by ephaptic coupling operates as a functional gate for external inputs, where weak stimuli are suppressed and sufficiently strong inputs are permitted to propagate. Notably, these complex behaviors emerge from a minimal framework governed by a single diffusion-mediated coupling constant, drawing a direct parallel to the large-scale synchronization principles observed in Dictyostelium discoideum . Cellular & Molecular Neuroscience ephaptic coupling action-potential synchronization cross-frequency synchronization functional gate for external inputs Full Text Additional Declarations The authors declare no competing interests. Supplementary Files Scheme.pdf Implementation Procedure for the Theory of Ephaptic Action-Potential Synchronization Cite Share Download PDF Status: Posted 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-9118948","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":605925905,"identity":"f9295c7b-8f1f-4a47-b0f8-7b21acf78d9b","order_by":0,"name":"Seido Nagano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYPACGwYJIHkAzGYGk2yEtKRBtBwgQcthsBaoNQSAOfvxi58LKs7bSzbwPjz84c/haH52BsYPPxj48nBpsezJKZaeceZ24mwGdoMDB9sO585sZmCW7GFgK8alxeBAToI0b9vtBDmg6w8cbDicu+EwA4M00C+JDbi0nH+T/Ju37Zw9WMuBP4dz9x9mYP6NV8uN9GNAWw4wzgZrYQPawszAht+WG2/YrHnOJCfObAZqOduWnjvjMGObZY8BHr+cT398m6fCzl7ieBvzh4o/1rn9/YcP3/hRcQxniDEw8BhAaGa4CCPQSQbHEnBrYX+AVbgGj5ZRMApGwSgYYQAAKLFX9DYv9rYAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-0948-0886","institution":"Ritsumeikan University","correspondingAuthor":true,"prefix":"","firstName":"Seido","middleName":"","lastName":"Nagano","suffix":""}],"badges":[],"createdAt":"2026-03-14 02:12:31","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9118948/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9118948/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104763842,"identity":"974418fd-a136-4504-a3cc-9fa90a3c4472","added_by":"auto","created_at":"2026-03-17 02:40:19","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":973227,"visible":true,"origin":"","legend":"","description":"","filename":"nagano3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9118948/v1_covered_c4a4bb75-4f22-4f68-b731-7bd2ea009759.pdf"},{"id":104763816,"identity":"2acf6019-ca35-4c7b-881b-db7fcb2f2f8d","added_by":"auto","created_at":"2026-03-17 02:40:13","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":89774,"visible":true,"origin":"","legend":"\u003cp\u003eImplementation Procedure for the Theory of Ephaptic Action-Potential Synchronization\u003c/p\u003e","description":"","filename":"Scheme.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9118948/v1/cc43bf6b55f12084bba4a25c.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eDiffusion-mediated nonlinear coupling drives ephaptic synchronization and Cross-Frequency Coordination\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Ritsumeikan University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ephaptic coupling, action-potential synchronization, cross-frequency synchronization, functional gate for external inputs","lastPublishedDoi":"10.21203/rs.3.rs-9118948/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9118948/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAction-potential synchronization mediated by ephaptic interactions poses a fundamental biophysical challenge: extracellular ionic fluctuations from a single spike are generally considered too small to significantly influence neighboring neurons. 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