Multi-Timescale Compound Oscillations in Pyramidal Neurons: Insights from a Three-Compartment Model

Multi-Timescale Compound Oscillations in Pyramidal Neurons: Insights from a Three-Compartment Model | 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 Multi-Timescale Compound Oscillations in Pyramidal Neurons: Insights from a Three-Compartment Model Feng Zhang, Meili Lu, Xile Wei This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4619904/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Sep, 2024 Read the published version in Nonlinear Dynamics → Version 1 posted 11 You are reading this latest preprint version Abstract Oscillation activities are widely observed in neurons and are critical to the brain's physiological functions. A significant phenomenon among these activities is the simultaneous presence of multiple oscillations at different frequencies, referred to as compound oscillations, which are particularly evident in epileptiform activity. However, the dynamical mechanisms underlying compound oscillations remain unknown. In this study, we develop and analyze a three-compartment pyramidal neuron model to address this problem. The model incorporates somatic Na+, dendritic Ca2+ and N-methyl-D-aspartate (NMDA)-mediated firing behaviors, capturing the multi-timescale dynamics essential for understanding compound oscillations. Phase-plane analysis reveals that Ca2+ firing behaviors in apical dendrite are relaxation oscillations, characterized by two timescales. Using geometric singular perturbation theory, we show that NMDA and Na+ firing behaviors involve three timescales. Specifically, NMDA firing behaviors in basal dendrite manifest as square-wave bursting, accompanied by Na+ action potentials in soma. Moreover, bifurcation analysis indicates that Ca2+ firing behaviors lead to the alternation of homoclinic bifurcation and saddle-node bifurcation on an invariant cycle (SNIC), which cause the occurrence and disappearance of bursting in basal dendrite. We also explore the impact of NMDA receptor conductance on these oscillatory patterns. Simulation results validate that impairment or excessive activation of NMDA receptors can lead to pathological compound oscillations, which have significant physiological implications. These insights gained from this model not only advance our understanding of neuronal function but also have potential implications for developing therapeutic strategies for neurological disorders characterized by compound oscillations. Compound oscillations Pyramidal neuron model Multi-timescale dynamics Fast-slow analysis Bifurcation theory Bursting Full Text Additional Declarations No competing interests reported. Supplementary Files supplymentmaterial.pdf Cite Share Download PDF Status: Published Journal Publication published 18 Sep, 2024 Read the published version in Nonlinear Dynamics → Version 1 posted Editorial decision: Revision requested 12 Jul, 2024 Reviews received at journal 12 Jul, 2024 Reviews received at journal 08 Jul, 2024 Reviews received at journal 05 Jul, 2024 Reviewers agreed at journal 03 Jul, 2024 Reviewers agreed at journal 30 Jun, 2024 Reviewers agreed at journal 27 Jun, 2024 Reviewers invited by journal 27 Jun, 2024 Editor assigned by journal 23 Jun, 2024 Submission checks completed at journal 22 Jun, 2024 First submitted to journal 21 Jun, 2024 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. 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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-4619904","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":325839415,"identity":"e6518c4c-bac9-4adc-aa0a-314cc455d910","order_by":0,"name":"Feng Zhang","email":"","orcid":"","institution":"Tianjin University","correspondingAuthor":false,"prefix":"","firstName":"Feng","middleName":"","lastName":"Zhang","suffix":""},{"id":325839417,"identity":"c8cdf330-450b-4804-911d-d457ff8cd386","order_by":1,"name":"Meili Lu","email":"","orcid":"","institution":"Tianjin University of Technology and Education","correspondingAuthor":false,"prefix":"","firstName":"Meili","middleName":"","lastName":"Lu","suffix":""},{"id":325839420,"identity":"dd2e9352-2e78-469d-a4c8-6d77a4ace956","order_by":2,"name":"Xile Wei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYDACZuYGICkhx8BwAEizEaWFEazFmId4LQxgLQyJPWAOMVoMjjM2PuapsEjfz3jGgOFD2WEG/tkN+LVINjM2G/OckcjtYThjwDjj3GEGiTsH8GvhZ2Zsk85tg2hh5m07zGAgkYBfCxszY/vv3H8S6TwgLX+J0QKyhTm3QSIBrIWRGC0gv0j/OSZh2HPgWMHBnnPpPBI3CGgxOH/44McZNXXy7DMOb3zwo8xajn8GAS0IIHEAHJk8xKoHAv4GEhSPglEwCkbBiAIAlTo+HT6SM9sAAAAASUVORK5CYII=","orcid":"","institution":"Tianjin University","correspondingAuthor":true,"prefix":"","firstName":"Xile","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2024-06-22 04:08:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4619904/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4619904/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11071-024-10289-4","type":"published","date":"2024-09-18T15:57:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":65103967,"identity":"ea6f0afa-0d1d-42a8-b1c7-500e5a4ec3a6","added_by":"auto","created_at":"2024-09-23 16:10:13","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6713271,"visible":true,"origin":"","legend":"","description":"","filename":"FengZhang.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4619904/v1_covered_48db57a5-6f60-40f7-bb32-e66218960e33.pdf"},{"id":60118712,"identity":"082d67f8-5097-4383-ba03-94d7de7feb9f","added_by":"auto","created_at":"2024-07-12 04:08:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1368605,"visible":true,"origin":"","legend":"","description":"","filename":"supplymentmaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4619904/v1/8d90c6caab17fd325bb6c376.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Multi-Timescale Compound Oscillations in Pyramidal Neurons: Insights from a Three-Compartment Model","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nonlinear-dynamics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nody","sideBox":"Learn more about [Nonlinear Dynamics](https://www.springer.com/journal/11071)","snPcode":"11071","submissionUrl":"https://submission.nature.com/new-submission/11071/3","title":"Nonlinear Dynamics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Compound oscillations, Pyramidal neuron model, Multi-timescale dynamics, Fast-slow analysis, Bifurcation theory, Bursting","lastPublishedDoi":"10.21203/rs.3.rs-4619904/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4619904/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Oscillation activities are widely observed in neurons and are critical to the brain's physiological functions. 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