Pericyte pannexin1 controls hippocampal capillary diameter and recognition memory

Pericyte pannexin1 controls hippocampal capillary diameter and recognition memory | 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 Pericyte pannexin1 controls hippocampal capillary diameter and recognition memory Sandra Mai-Morente, Eugenia Isasi, Alberto Rafael, Silvia Olivera-Bravo, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3832782/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Jul, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract In the brain-blood-barrier, contractile pericytes fine-tune the capillary resistance and blood supply to meet neuro-metabolic demands; molecular players governing these functions remain undefined. The protein subunit pannexin1 (Panx1), assembles into transmembrane large-pore hemichannels (Panx1HCs) mediating the release of ATP, a regulator of pericyte contractility and capillary resistance. Until now, the expression and role of pericyte Panx1 in brain physiology were unknown. Here, we report that cerebral pericytes express functional Panx1HCs. Pericyte-specific Panx1 is required for recognition memory and hippocampal capillary dilation induced by pharmacological activation of glutamatergic synaptic transmission, which underlies functional hyperaemia. Mechanistically, pericyte Panx1 is modulated by glutamatergic NMDA/AMPA and purinergic P2X7/P2Y6 receptors and controls ATP release influencing pericyte Ca 2+ and hippocampal capillary diameter dynamics. Our study unveils pericyte Panx1 as a novel physiological regulator of cerebral capillary resistance, crucial for sustaining higher brain functions and a potential therapeutic target for cognitive disorders associated with cerebrovascular diseases. Biological sciences/Neuroscience/Neuro–vascular interactions Biological sciences/Physiology/Neurophysiology pericytes pannexin1 hemichannels ATP capillaries neurovascular cognition Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 03 Jul, 2025 Read the published version in Nature Communications → 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-3832782","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":266541904,"identity":"7aa1d023-b692-4ebb-9779-1627a31c4110","order_by":0,"name":"Sandra Mai-Morente","email":"","orcid":"https://orcid.org/0009-0003-1513-743X","institution":"Universidad de la República O. del Uruguay","correspondingAuthor":false,"prefix":"","firstName":"Sandra","middleName":"","lastName":"Mai-Morente","suffix":""},{"id":266541905,"identity":"7b3a1821-42cd-4e0d-90e7-3a583d769f01","order_by":1,"name":"Eugenia 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The protein subunit pannexin1 (Panx1), assembles into transmembrane large-pore hemichannels (Panx1HCs) mediating the release of ATP, a regulator of pericyte contractility and capillary resistance. Until now, the expression and role of pericyte Panx1 in brain physiology were unknown.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHere, we report that cerebral pericytes express functional Panx1HCs. Pericyte-specific Panx1 is required for recognition memory and hippocampal capillary dilation induced by pharmacological activation of glutamatergic synaptic transmission, which underlies functional hyperaemia. Mechanistically, pericyte Panx1 is modulated by glutamatergic NMDA/AMPA and purinergic P2X7/P2Y6 receptors and controls ATP release influencing pericyte Ca\u003csup\u003e2+\u003c/sup\u003e and hippocampal capillary diameter dynamics.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study unveils pericyte Panx1 as a novel physiological regulator of cerebral capillary resistance, crucial for sustaining higher brain functions and a potential therapeutic target for cognitive disorders associated with cerebrovascular diseases.\u003c/p\u003e","manuscriptTitle":"Pericyte pannexin1 controls hippocampal capillary diameter and recognition memory","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-16 01:49:33","doi":"10.21203/rs.3.rs-3832782/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"6c1ef291-97f2-4035-b3ea-eb6f61ae566c","owner":[],"postedDate":"January 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":28093501,"name":"Biological sciences/Neuroscience/Neuro\u0026#x2013;vascular interactions"},{"id":28093502,"name":"Biological sciences/Physiology/Neurophysiology"}],"tags":[],"updatedAt":"2025-07-04T07:05:55+00:00","versionOfRecord":{"articleIdentity":"rs-3832782","link":"https://doi.org/10.1038/s41467-025-61312-0","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2025-07-03 04:00:00","publishedOnDateReadable":"July 3rd, 2025"},"versionCreatedAt":"2024-01-16 01:49:33","video":"","vorDoi":"10.1038/s41467-025-61312-0","vorDoiUrl":"https://doi.org/10.1038/s41467-025-61312-0","workflowStages":[]},"version":"v1","identity":"rs-3832782","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3832782","identity":"rs-3832782","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}