Brain-wide Organization of Post-Synaptic Sites: Three Principles

Brain-wide Organization of Post-Synaptic Sites: Three Principles | 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 Brain-wide Organization of Post-Synaptic Sites: Three Principles Hanchuan Peng, Yina Wei, Yuze Liu, Feng Xiong, Fuhui Long This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8484258/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 Synapses are fundamental units of neural computation and structural plasticity in the brain, yet their brain-wide spatial organization in mammals remains largely unknown. Building on our previous mapping and modeling of dendritic spines and axonal boutons, we developed a statistical approach to generate over 17.99 million predicted post-synaptic sites based on the potential arbor contacts (PPSSPAC) across the dendritic arbors of 155,743 neurons spanning the entire mouse brain. By analyzing the topological features of these sites, we identified three key organizational principles. First, PPSSPAC exhibits a distinct region-specific spatial pattern at the dendritic branch level, preferentially enriching near the distal ends of dendritic segments, in contrast to the valley-like distribution of pre-synaptic sites along axonal branches. Cross-species validation against independent electron microscopy datasets from mouse and human brains, revealed a conserved and previously unquantified pattern of synaptic organization. Second, the spatial distribution of PPSSPAC effectively captures variations across cell types in the hippocampus, enabling neuron classification based on synaptic architecture. This serves as a complementary mesoscale descriptor to existing classifications based on global neuronal connectivity (source-target relationships) or local dendritic microenvironments. Third, the spatial distribution of PPSSPAC, rather than synapse density, shows remarkable correlation with independent whole-brain electrophysiological activity. The spatial organization of PPSSPAC also correlates with several gene expression datasets. These results suggest the post-synaptic pattern could be mediator linking molecular signatures, neural dynamics, and connectivity types of cells. Our study reveals, for the first time, a structural substrate for hierarchical information processing in the brain, providing new insights into neural computation and a foundation for brain digital twin models to support next-generation AI infrastructure. Biological sciences/Neuroscience Biological sciences/Computational biology and bioinformatics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files STable1155kDENsomafeature.csv Supplementary Table 1 STable2ppssfrompacsummary.csv Supplementary Table 2 STable3searchbestdist.csv Supplementary Table 3 STable4GPTannotation.csv Supplementary Table 4 STable5ppssfrompbsummary.csv Supplementary Table 5 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. 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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-8484258","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":589809665,"identity":"14f44505-6d02-4118-b5b2-1857f5875360","order_by":0,"name":"Hanchuan 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