Mouse Brain Atlas of Dendritic Microenvironments Identifies Associations of Anatomy, Projection Targets and Transcriptomic Profiles of Neurons

Mouse Brain Atlas of Dendritic Microenvironments Identifies Associations of Anatomy, Projection Targets and Transcriptomic Profiles of Neurons | 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 Mouse Brain Atlas of Dendritic Microenvironments Identifies Associations of Anatomy, Projection Targets and Transcriptomic Profiles of Neurons Hanchuan Peng, Yufeng Liu, Sujun Zhao, Zhixi Yun, Feng Xiong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5117895/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Nov, 2025 Read the published version in Nature Neuroscience → Version 1 posted You are reading this latest preprint version Abstract Digital brain atlases have become essential anatomical references for understanding the spatial and functional organization of brains. For mice, typical resources include the Allen Reference Atlas, the Allen Common Coordinate Framework (CCF), and their variants, like CCFv3. However, previous whole-brain atlases were constructed based on limited neuronal features, such as cell body (soma) density or average maps from collections of registered brain images, without considering the spatial organization of neuronal arbors. This study introduces a microenvironment representation that incorporates the morphological features of neighboring neurons to better quantify brain modularity. We generated a large dataset containing dendrites from 101,136 neurons across 111 mouse brains, covering 91% of non-ventricular, non-fiber-tract CCF regions, and constructed a multidimensional microenvironment feature map of the whole brain. Our findings reveal that the spatial organization of these microenvironments outperforms the CCFv3 and a state-of-the-art spatial transcriptomic cell atlas by providing complementary subregions within established regions, nearly doubling the total number of brain regions compared to CCFv3. In this way, our atlas enables the identification of previously unobserved neuron groupings or “subtypes”. Our results also demonstrate that this microenvironment atlas enhances local spatial homogeneity while maintaining spatial differentiation within established CCF brain regions. For example, we found that the microenvironments of hippocampal neurons are correlated with axonal projection targets and improve the specificity of projection mapping, which implies the potential characterization of long-range axonal projections of mammalian neurons based on only local dendritic organization. The sub-parcellation of the caudoputamen (CP) aligns well with previous studies on projections, connectivity, and transcriptomics, revealing diverse input and output wiring patterns among CP subregions. Biological sciences/Neuroscience Biological sciences/Computational biology and bioinformatics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files brainsupplt1.csv Supplementary Table 1 Cite Share Download PDF Status: Published Journal Publication published 24 Nov, 2025 Read the published version in Nature Neuroscience → 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-5117895","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":365091411,"identity":"c66b10fe-0f15-40f2-bc87-5c229227aff8","order_by":0,"name":"Hanchuan 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