Astrocytes provide the temporal dynamic required for memory formation

Astrocytes provide the temporal dynamic required for memory formation | 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 Biological Sciences - Article Astrocytes provide the temporal dynamic required for memory formation Jean-Francois Perrier, Silas Larsen, Nikolaj Hansen, Konstantin Khodosevich, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5416477/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 Theta oscillations (4-12 Hz) in the hippocampus, driven by synchronous neuronal bursts, are essential for grouping and selecting neuronal ensembles during spatial navigation, memory, and learning 1,2. Yet, the specific mechanisms enabling this frequency band to effectively modulate neuronal ensembles remain unclear. Here, we show that burst activity at the CA3-CA1 synapse in the mouse hippocampus initiates rapid activation of astrocytic leaflets. This activation is mediated by retrograde messengers, which in turn activate transient receptor potential channels in astrocytes, potentiating glutamate release from Schaffer collaterals via the activation of presynaptic glutamate receptors. We show that this mechanism is synapse-specific and necessary for the induction of long-term potentiation (LTP). Remarkably, this positive feedback loop peaks 50 to 200 ms after a burst, precisely aligning with the theta frequency range and optimizing reinforcement of neuronal activity. These findings indicate that astrocytes provide critical timing to potentiate synaptic transmission during the initial phases of learning and memory formation. Biological sciences/Neuroscience/Cellular neuroscience Biological sciences/Neuroscience/Learning and memory/Hippocampus Full Text Additional Declarations There is NO Competing Interest. 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5416477","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":383523993,"identity":"0ecb7654-d29e-498d-88a5-e40c70fcc863","order_by":0,"name":"Jean-Francois Perrier","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYLCCBAYGORAtwXAASJ4hUosxiVqAILGBaC3m7L3PPjyouJc+f0buwRsMZw4z8J05gF+LZc9x4xkJZ4pzN9zIS7ZguHGYQfJsA34tBjfSmBkS2xJyN0jkmEkwfDjMYHCegMMM7j8DavmXkC4/g2gtN9iAWhoSEhhugLQAHWZAyGGWPUCHJRxLMNxw5o2xRcKZdB5JQt43Zz/GzPijJkFevj3H8MaHY9ZyfGcSCDgMhQdUzEPAJ+haRsEoGAWjYBRgAwDZSEWVjSiuWAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-9189-3574","institution":"University of Copenhagen","correspondingAuthor":true,"prefix":"","firstName":"Jean-Francois","middleName":"","lastName":"Perrier","suffix":""},{"id":383523994,"identity":"08bdc642-5af9-4958-a3d3-4c0d11be7ccc","order_by":1,"name":"Silas Larsen","email":"","orcid":"","institution":"University of Copenhagen","correspondingAuthor":false,"prefix":"","firstName":"Silas","middleName":"","lastName":"Larsen","suffix":""},{"id":383523995,"identity":"2d7d4647-09e0-4e93-962a-9a1129506022","order_by":2,"name":"Nikolaj Hansen","email":"","orcid":"","institution":"Copenhagen University","correspondingAuthor":false,"prefix":"","firstName":"Nikolaj","middleName":"","lastName":"Hansen","suffix":""},{"id":383523996,"identity":"29f15eec-ac6e-4fc6-b51a-aa7e2c137a7a","order_by":3,"name":"Konstantin Khodosevich","email":"","orcid":"https://orcid.org/0000-0001-7232-5558","institution":"University of Copenhagen","correspondingAuthor":false,"prefix":"","firstName":"Konstantin","middleName":"","lastName":"Khodosevich","suffix":""},{"id":383523997,"identity":"da13d001-33ea-4b7f-9fc8-82a6b7352e97","order_by":4,"name":"Navneet Vasistha","email":"","orcid":"","institution":"University of Copenhagen","correspondingAuthor":false,"prefix":"","firstName":"Navneet","middleName":"","lastName":"Vasistha","suffix":""}],"badges":[],"createdAt":"2024-11-08 12:21:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5416477/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5416477/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73238516,"identity":"edd1de92-6646-4cdd-bf1c-57b760531ec2","added_by":"auto","created_at":"2025-01-08 05:38:20","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":917967,"visible":true,"origin":"","legend":"Article File","description":"","filename":"202411108Larsenetal.submittedversion.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5416477/v1_covered_cc01115d-b68e-408a-914c-3f0b8195547b.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Astrocytes provide the temporal dynamic required for memory formation","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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-5416477/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5416477/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Theta oscillations (4-12 Hz) in the hippocampus, driven by synchronous neuronal bursts, are essential for grouping and selecting neuronal ensembles during spatial navigation, memory, and learning 1,2. 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