Detangling the spinal respiratory network’s responses to cervical epidural stimulation after spinal cord injury

Detangling the spinal respiratory network’s responses to cervical epidural stimulation after spinal cord injury | 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 Detangling the spinal respiratory network’s responses to cervical epidural stimulation after spinal cord injury Alyssa Mickle, Jesús Peñaloza-Aponte, Caitlin Brennan, Erica Dale This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8853409/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Respiratory insufficiency is the leading cause of mortality after spinal cord injury, yet current pacing strategies override brainstem rhythm generators, limiting adaptability and rehabilitation. Electrical stimulation of the spinal cord in the locomotor system enables volitional patterned movements after injury by activating spinal central pattern generators. However, as the central pattern generators for breathing lie in the brainstem, it is unclear what neural populations are acted upon by electrical stimulation of the cervical spinal cord. In anesthetized rats with cervical injury, we compared inspiratory-triggered, expiratory-triggered, and open-loop stimulation under varying descending inputs. All stimulation patterns elicit diaphragm motor output, but descending inputs and spinal inhibition are necessary to achieve appropriate endogenous respiratory patterning. Short-latency responses and increased immediate early gene expression indicated recruitment of local spinal interneurons, including inhibitory populations. This furthers our understanding of the respiratory neural populations epidural stimulation interacts with and highlights the necessity of inspiratory-patterned stimulation. Health sciences/Diseases/Neurological disorders/Spinal cord diseases Biological sciences/Neuroscience/Motor control/Spinal cord Full Text Additional Declarations There is NO Competing Interest. Supplementary Files finaleditsAOextendeddata20250210.docx Extended data for 'Detangling the spinal respiratory network’s responses to cervical epidural stimulation after spinal cord injury' Cite Share Download PDF Status: Under Review 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. 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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-8853409","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":593352203,"identity":"f08ff168-3413-45c9-a2e1-e504de0456b1","order_by":0,"name":"Alyssa Mickle","email":"","orcid":"","institution":"University of Florida","correspondingAuthor":false,"prefix":"","firstName":"Alyssa","middleName":"","lastName":"Mickle","suffix":""},{"id":593352204,"identity":"10b7b58d-64e4-4dc3-96ac-c3fa0593c8c7","order_by":1,"name":"Jesús Peñaloza-Aponte","email":"","orcid":"https://orcid.org/0000-0001-5903-2291","institution":"University of Florida","correspondingAuthor":false,"prefix":"","firstName":"Jesús","middleName":"","lastName":"Peñaloza-Aponte","suffix":""},{"id":593352205,"identity":"1c481dd4-c5f3-41f8-9c6a-971b3d41ed25","order_by":2,"name":"Caitlin Brennan","email":"","orcid":"","institution":"University of Florida","correspondingAuthor":false,"prefix":"","firstName":"Caitlin","middleName":"","lastName":"Brennan","suffix":""},{"id":593352202,"identity":"d3261257-f004-4c67-82ca-20c4523e60d0","order_by":3,"name":"Erica Dale","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYFACxgYGBjYGGQb2BoYPDyBc4rTwMPAcYJyRQJwWEABpkUggUgu/9OHGDz/K7Hj4Jd8YNiQw2MhuOEBAi2RfYrNkz7lkHsnZOSAtacYEtRicYWxj4G1j5jG4nWP+IIHhcCJBLfZALYx/2+p57G+eAdnyn7AWAx7GNmbetsM8BhI8IC0HCGuROMPYLC1z7jiPxJm0woYEg2TjmYS08PewP/z4pqxajr/98MaGDxV2sn2EtKC7kzTlo2AUjIJRMApwAAAiq0Fju+NeMwAAAABJRU5ErkJggg==","orcid":"","institution":"University of Florida","correspondingAuthor":true,"prefix":"","firstName":"Erica","middleName":"","lastName":"Dale","suffix":""}],"badges":[],"createdAt":"2026-02-11 15:26:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8853409/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8853409/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106404714,"identity":"9f192c5b-904e-4cdd-8c42-696c866ed1d9","added_by":"auto","created_at":"2026-04-08 09:16:38","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6878973,"visible":true,"origin":"","legend":"","description":"","filename":"finaleditsAOpaper20250210.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8853409/v1_covered_83cd727b-56ae-4809-8364-1783d35fc8b4.pdf"},{"id":106008651,"identity":"c4765d31-f2e5-454a-a2b8-c74a3dc1df87","added_by":"auto","created_at":"2026-04-02 11:16:01","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24138598,"visible":true,"origin":"","legend":"Extended data for 'Detangling the spinal respiratory network\u0026#x2019;s responses to cervical epidural stimulation after spinal cord injury'","description":"","filename":"finaleditsAOextendeddata20250210.docx","url":"https://assets-eu.researchsquare.com/files/rs-8853409/v1/7285267ce9c166544fa4b902.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Detangling the spinal respiratory network’s responses to cervical epidural stimulation after spinal cord injury","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":true,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8853409/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8853409/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Respiratory insufficiency is the leading cause of mortality after spinal cord injury, yet current pacing strategies override brainstem rhythm generators, limiting adaptability and rehabilitation. 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