Transcranial Alternating Current Stimulation Improves Post-Anesthesia Motor Function in Aged Mice via Dual striatal Pathways: Dopamine Release and THIN Activation

Transcranial Alternating Current Stimulation Improves Post-Anesthesia Motor Function in Aged Mice via Dual striatal Pathways: Dopamine Release and THIN Activation | 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 Transcranial Alternating Current Stimulation Improves Post-Anesthesia Motor Function in Aged Mice via Dual striatal Pathways: Dopamine Release and THIN Activation Honggang Zang, Wanxia Xie, Xing Wang, Lei Tian, Xiaolong Liu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8952340/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background: Transcranial alternating current stimulation (tACS) enhances motor performance, but its subcortical mechanisms in aged populations remain unclear. We investigated whether 20 Hz tACS over M1 engages striatal circuitry in aged mice under sevoflurane anesthesia via two parallel mechanisms: nigrostriatal dopamine release and THIN activation. Methods: Aged mice received 20 Hz tACS (0.15 mA, 20 min/day) or sham over M1 for seven days under sevoflurane. Motor performance was assessed by single‑pellet reaching task. Analyses included: FSCV for dopamine release; Golgi staining for spine density; c‑Fos/TH for THIN activation; EEG and cortical blood flow (CBF). Optogenetic gain‑of‑function with selective 20 Hz THIN activation was performed in a separate cohort. Results:tACS improved post‑anesthesia reaching success (p < 0.05), enhanced dopamine release (p < 0.01), THIN activation (p < 0.01), spine density (p < 0.01), and β‑band oscillations (p < 0.01). Optogenetic THIN activation recapitulated motor and β‑band enhancement (both p < 0.01), but not CBF increase. Conclusion: 20 Hz tACS enhances motor function in aged mice under sevoflurane via dopamine‑dependent plasticity and THIN‑mediated oscillatory modulation, identifying THINs as a key cellular substrate for tACS‑induced motor tACS Aging Anesthesia Motor function THINs Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 31 Mar, 2026 Reviewers agreed at journal 30 Mar, 2026 Reviewers invited by journal 24 Mar, 2026 Editor invited by journal 27 Feb, 2026 Editor assigned by journal 24 Feb, 2026 Submission checks completed at journal 24 Feb, 2026 First submitted to journal 23 Feb, 2026 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. 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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-8952340","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":611698192,"identity":"97a33997-33c9-4b5a-88da-25326a2214c7","order_by":0,"name":"Honggang Zang","email":"","orcid":"","institution":"The First Hospital of Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"Honggang","middleName":"","lastName":"Zang","suffix":""},{"id":611698195,"identity":"f075a666-270d-4b16-960e-a5c1dbcc262a","order_by":1,"name":"Wanxia 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Activation","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"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":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"tACS,Aging,Anesthesia, Motor function,THINs","lastPublishedDoi":"10.21203/rs.3.rs-8952340/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8952340/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Transcranial alternating current stimulation (tACS) enhances motor performance, but its subcortical mechanisms in aged populations remain unclear. We investigated whether 20 Hz tACS over M1 engages striatal circuitry in aged mice under sevoflurane anesthesia via two parallel mechanisms: nigrostriatal dopamine release and THIN activation.\u003c/p\u003e\n\u003cp\u003eMethods: Aged mice received 20 Hz tACS (0.15 mA, 20 min/day) or sham over M1 for seven days under sevoflurane. Motor performance was assessed by single‑pellet reaching task. Analyses included: FSCV for dopamine release; Golgi staining for spine density; c‑Fos/TH for THIN activation; EEG and cortical blood flow (CBF). Optogenetic gain‑of‑function with selective 20 Hz THIN activation was performed in a separate cohort.\u003c/p\u003e\n\u003cp\u003eResults:tACS improved post‑anesthesia reaching success (p \u0026lt; 0.05), enhanced dopamine release (p \u0026lt; 0.01), THIN activation (p \u0026lt; 0.01), spine density (p \u0026lt; 0.01), and β‑band oscillations (p \u0026lt; 0.01). Optogenetic THIN activation recapitulated motor and β‑band enhancement (both p \u0026lt; 0.01), but not CBF increase.\u003c/p\u003e\n\u003cp\u003eConclusion: 20 Hz tACS enhances motor function in aged mice under sevoflurane via dopamine‑dependent plasticity and THIN‑mediated oscillatory modulation, identifying THINs as a key cellular substrate for tACS‑induced motor\u003c/p\u003e","manuscriptTitle":"Transcranial Alternating Current Stimulation Improves Post-Anesthesia Motor Function in Aged Mice via Dual striatal Pathways: Dopamine Release and THIN Activation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-26 09:43:25","doi":"10.21203/rs.3.rs-8952340/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-31T11:39:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"212791896414819028991526968152428206638","date":"2026-03-30T10:20:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-24T16:25:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-27T14:58:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-24T06:58:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-24T06:57:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2026-02-24T03:49:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e17b9335-18db-4523-9a48-ce045266d0b4","owner":[],"postedDate":"March 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-26T09:43:25+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-26 09:43:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8952340","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8952340","identity":"rs-8952340","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}