Activation of α2A-adrenergic receptors promotes facial stimulation-induced cerebellar MLI-PC LTD and motor learning in vivo in mice

Activation of α2A-adrenergic receptors promotes facial stimulation-induced cerebellar MLI-PC LTD and motor learning in vivo in mice | 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 Activation of α2A-adrenergic receptors promotes facial stimulation-induced cerebellar MLI-PC LTD and motor learning in vivo in mice Wen-Cai Weng, Xu-Dong Zhang, Jun-Ya Wang, Ming-Ze Sun, Chao-Yue Chen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6514206/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Jul, 2025 Read the published version in The Cerebellum → Version 1 posted 9 You are reading this latest preprint version Abstract The α2-adrenergic receptor (α2-AR) is involved in various information transmission processes in the cerebellar cortex, but the role of AR in modulating the sensory stimulation-induced synaptic plasticity remains unclear. Here, we investigated the role of α2-AR during the facial stimulation-evoked cerebellar molecular layer interneuron-Purkinje cell (MLI-PC) long-term synaptic plasticity and motor learning in vivo in mice, using electrophysiological, pharmacological, immunohistochemical, and rotarod test methods. Our results demonstrated that 1 Hz facial stimulation induced MLI-PC long-term depression (LTD), which was significantly enhanced by microinjection of noradrenaline (NA) into cerebellar molecular layer. Blockade of the NMDA receptor abolished the facial stimulation-induced MLI-PC LTD, whereas activation of AR with NA or activation α2-AR with UK14304 triggered 1 Hz facial stimulation-induced MLI-PC LTD in absence NMDA receptor activity. Furthermore, α2-AR activation-triggered 1 Hz facial stimulation-induced MLI-PC LTD was abolished by blockade of α2A-, but not α2B- or α2C-ARs. The facial stimulation-induced MLI-PC LTD was triggered by a selective α2A-AR agonist, guanfacine, but it was completely prevented by inhibition of protein kinase A (PKA) with KT5720. The rotarod test indicated that microinjection of guanfacine onto cerebellar cortex to activate α2A-AR significantly improved initial motor learning ability of mice. The immunohistochemistry study showed that the immunoreactivity of α2A-AR was expressed in the mouse cerebellar cortex, mostly in the PC layer and MLIs. These results suggest that NA triggers the facial stimulation-induced an α2A-AR/PKA signaling cascade-dependent MLI-PC LTD and promotes the acquisition of motor learning in mice. Sensory stimulation in vivo cell-attached recording molecular layer interneuron-Purkinje cell long-term depression (MLI-PC LTD) α2-adrenergic receptors protein kinase A motor learning Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Jul, 2025 Read the published version in The Cerebellum → Version 1 posted Editorial decision: Revision requested 01 Jun, 2025 Reviews received at journal 22 May, 2025 Reviews received at journal 21 May, 2025 Reviewers agreed at journal 02 May, 2025 Reviewers agreed at journal 01 May, 2025 Reviewers invited by journal 28 Apr, 2025 Editor assigned by journal 25 Apr, 2025 Submission checks completed at journal 25 Apr, 2025 First submitted to journal 23 Apr, 2025 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-6514206","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":449594651,"identity":"c400300f-716c-427d-a3e1-dd6a3e15e63f","order_by":0,"name":"Wen-Cai Weng","email":"","orcid":"","institution":"Yanbian University","correspondingAuthor":false,"prefix":"","firstName":"Wen-Cai","middleName":"","lastName":"Weng","suffix":""},{"id":449594652,"identity":"e348cc40-b1e5-418f-b0d7-b96c5b36dabb","order_by":1,"name":"Xu-Dong Zhang","email":"","orcid":"","institution":"Yanbian 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