{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:37:38Z","timestamp":1785404258647,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,8]]},"group-title":"Neuroscience","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["U24NS139927"],"award-info":[{"award-number":["U24NS139927"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R24MH114785"],"award-info":[{"award-number":["R24MH114785"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,8]]},"abstract":"<jats:p>Neurons interact at synapses, but they also communicate through physical contact and proximity, including diffusion, glia-mediated interactions, and ephaptic coupling. Standard connectomes map synapses, but cannot capture the full set of cell-cell contacts that can support these pathways. Here we extract contactomes from two large mouse visual cortex volumes at nanoscale resolution and quantify every cell-cell contact, the shared surface area of each contact, and the relationship between contact and synaptic connectivity. We find that contactomes are 5 to 10 times denser than synaptic graphs, revealing that neurons physically contact a much larger set of potential neighbors than they synaptically connect to. We further find that most nearby potential neighbors are already in physical contact, indicating that local structural change would add few new candidate synaptic partners. Finally, we find that astrocytes form a single large syncytium-like network that spans the tissue and directly contacts nearly all neurons, and that glial processes lie within a micron or two of almost every synapse, indicating that synapses reside within a pervasive glia-shaped microenvironment. Together, these results show that physical contact forms a distinct layer of brain architecture that extends far beyond the synaptic connectome<\/jats:p>","DOI":"10.64898\/2026.05.08.723866","type":"posted-content","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:40:14Z","timestamp":1778312414000},"source":"Crossref","is-referenced-by-count":0,"title":["Physical contact reveals a hidden layer of cortical architecture"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9470-760X","authenticated-orcid":false,"given":"Jordan K","family":"Matelsky","sequence":"first","affiliation":[{"name":"Research & Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4561-1203","authenticated-orcid":false,"given":"Hannah","family":"Martinez","sequence":"additional","affiliation":[{"name":"Research & Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Robinette","sequence":"additional","affiliation":[{"name":"Research & Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9593-4312","authenticated-orcid":false,"given":"Katharine","family":"Merfeld","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4812-0120","authenticated-orcid":false,"given":"Daniel","family":"Xenes","sequence":"additional","affiliation":[{"name":"Research & Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara J.","family":"Cavanaugh","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9587-3784","authenticated-orcid":false,"given":"Sarah E.","family":"Emerson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-3101","authenticated-orcid":false,"given":"Dhananjay","family":"Bhaskar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0306-3184","authenticated-orcid":false,"given":"Benjamin","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5509-3734","authenticated-orcid":false,"given":"Caitlyn","family":"Bishop","sequence":"additional","affiliation":[{"name":"Research & Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8408-4499","authenticated-orcid":false,"given":"Konrad P.","family":"Kording","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania, 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USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1500-2143","authenticated-orcid":false,"given":"Brock","family":"Wester","sequence":"additional","affiliation":[{"name":"Research & Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.08.723866","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:40:14Z","timestamp":1778312414000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.08.723866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.05.08.723866","relation":{},"subject":[],"published":{"date-parts":[[2026,5,8]]},"subtype":"preprint"}}