Circuit-specific proteome remodelling controls remote-memory recall

Circuit-specific proteome remodelling controls remote-memory recall | 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 Circuit-specific proteome remodelling controls remote-memory recall Tetsuya Takano, Sayaka Nagamoto, Yuki Ito, Akari Fukuda, Junpei Matsubayashi, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8597698/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The mechanisms by which circuit-specific presynaptic molecular architectures in long-range pathways facilitate the transition from recent to remote memory remain unclear, even though this transition is central to systems-level consolidation and is relevant to both neuropsychiatric and neurodevelopmental disorders. In this study, we introduce an activity-dependent presynaptic BioID strategy, Active Neuron-specific Projection-eXclusive BioID (ActProX-ID), to define how recall activated presynaptic proteomes at the medial prefrontal cortex (mPFC)–basolateral amygdala (BLA) synapses are remodelled during both recent and remote fear recall. ActProX-ID uncovers presynaptic network reconfiguration between recall phases, identifies synaptic and trafficking modules that are differentially engaged as memories mature, and highlights disease-associated proteins whose orthologues exhibit conserved expression in the marmoset prefrontal cortex. Tetraspanin-7 (TSPAN7) is an activity-regulated protein that accumulates at remote recall-activated mPFC–BLA synapses and associates with complexin-2 (CPLX2) to facilitate SNARE-dependent vesicle recycling. Circuit-specific deletion of TSPAN7 or expression of the neurodevelopmental disease-linked TSPAN7 P172H variant disrupts remote contextual fear memory and socioemotional behaviour in mice. Here we show that recall-dependent presynaptic remodelling in the prefrontal–amygdala pathway supports the stabilisation of remote fear memory during system consolidation and implicate a TSPAN7–CPLX2 module in the socioemotional effects of human risk variants. Biological sciences/Molecular biology/Proteomics Biological sciences/Neuroscience/Molecular neuroscience Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTable6.docx Supplementary Table 6 SupplementaryTable3.xlsx Supplementary Table 3 SupplementaryTable2.xlsx Supplementary Table 2 SupplementaryTable5.xlsx Supplementary Table 5 ExtendedDataTable2.xlsx Extended Data Table 2 SupplementaryTable7.xlsx Supplementary Table 7 SupplementaryTable8.xlsx Supplementary Table 8 ExtendedDataTable3.xlsx Extended Data Table 3 ExtendedDataTable1.xlsx Extended Data Table 1 SupplementalFig.1.pdf Full-size images of immunoblots. SupplementaryTable1.xlsx Supplementary Table 1 SupplementaryTable4.xlsx Supplementary Table 4 ExtendedDataFigures.pdf Extended Data Figures 1-9 Cite Share Download PDF Status: Posted 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. 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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-8597698","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":598367302,"identity":"1ca0bd3b-ef21-4e94-9db6-2e3b25148cdc","order_by":0,"name":"Tetsuya 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