Threat intensity shapes cortical engram architecture supporting remote memory retrieval

Threat intensity shapes cortical engram architecture supporting remote memory retrieval | 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 Threat intensity shapes cortical engram architecture supporting remote memory retrieval Michel van den Oever, Miodrag Mitric, Sanne Beerens, Panthea Nemat, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6920860/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 The strength of persistent threat memories depends on the intensity of an aversive experience. We combined engram tagging with chemogenetics, electrophysiology and structural spine analyses to identify how threat intensity, following mild or strong contextual threat conditioning (CTC), shapes maturation of prelimbic cortex (PL) pyramidal engram neurons. PL engram cells mediate retrieval of mild, but not strong, remote threat memories, and develop neuroadaptations that are time-dependent, dendritic segment-specific, and modulated by threat intensity. Specifically, mild CTC increased synaptic connectivity by addition of long thin spines on oblique dendrites of engram neurons. Increased presynaptic release probability, together with reduced postsynaptic strength and spine size, developed regardless of threat intensity. Excitability was reduced in strong CTC-activated PL neurons without an increase in synaptic connectivity, supporting their functional disengagement. Our findings reveal how threat intensity shapes cortical engram architecture, which is pivotal for understanding the neural representation of threat memory strength and persistence. Biological sciences/Neuroscience/Learning and memory/Fear conditioning Biological sciences/Neuroscience/Spine regulation and structure Learning Engram Trauma Fear Prefrontal cortex c-Fos Synaptic strength Structural plasticity TRAP Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplinfoMitricBeerensetal.pdf Supplementary info SourceData.xlsx Source Data file 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-6920860","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":476195971,"identity":"75e5a134-2859-4bc6-9e5d-cf4b6b33fe0b","order_by":0,"name":"Michel van den Oever","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIiWNgGAWjYDACZgY2BoYCMNMAJsb4AETy4dVigKqFGcxiw20PphY2CXxadNuZnz34YMCQ2D+7eePjAgYbOYPjvc+qedsY8nBpMTvMZm44A6hlxp1jxcYzGNKMDc4cN7sN1FKMWwsPmzSPAYMxw40cM2kehsOJM2eksd2c2caQ2IZPyx+gFvkbOea/gVrqZ85/xlZIUAvQ43IGQFuYgVoS+CXY2Bg+4tXCZibZYyAhZ3gjrRjowjTDfp40ZokP5yRwazl/+JnEjwobHrkbyRs/81TYyLOxH2P8kFBmk9iPQwsUSEBpAwyRUTAKRsEoGAXkAABAvUleP4u45gAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-5523-8612","institution":"Vrije Universiteit Amsterdam","correspondingAuthor":true,"prefix":"","firstName":"Michel","middleName":"van den","lastName":"Oever","suffix":""},{"id":476195972,"identity":"2b628e9b-6375-4fa6-a7cf-07b306d4854d","order_by":1,"name":"Miodrag Mitric","email":"","orcid":"https://orcid.org/0000-0003-4137-3375","institution":"Vrije Universiteit Amsterdam","correspondingAuthor":false,"prefix":"","firstName":"Miodrag","middleName":"","lastName":"Mitric","suffix":""},{"id":476195973,"identity":"6261319c-ef1d-43f1-8f63-f6fdb3195467","order_by":2,"name":"Sanne Beerens","email":"","orcid":"","institution":"Vrije Universiteit Amsterdam","correspondingAuthor":false,"prefix":"","firstName":"Sanne","middleName":"","lastName":"Beerens","suffix":""},{"id":476195974,"identity":"24a584c1-fefa-463e-9bd4-0eaa32f285cf","order_by":3,"name":"Panthea Nemat","email":"","orcid":"","institution":"Dept. 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