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Vagal sensory neurons (VSNs) form an important body-to-brain connection, navigating visceral organs along the rostral\u2013caudal axis of the body and crossing the surface\u2013lumen axis of organs into appropriate tissue layers\n                    <jats:sup>5,6<\/jats:sup>\n                    . The brain can discriminate numerous body signals through VSNs, but the underlying coding strategy remains poorly understood. Here we show that VSNs code visceral organ, tissue layer and stimulus modality\u2014three key features of an interoceptive signal\u2014in different dimensions. Large-scale single-cell profiling of VSNs from seven major organs\u00a0in mice using multiplexed projection barcodes reveals a \u2018visceral organ\u2019 dimension composed of differentially expressed gene modules that code organs along the body\u2019s rostral\u2013caudal axis. We discover another \u2018tissue layer\u2019 dimension with gene modules that code the locations of VSN endings along the surface\u2013lumen axis of organs. Using calcium-imaging-guided spatial transcriptomics, we show that VSNs are organized into functional units to sense similar stimuli across organs and tissue layers; this constitutes a third \u2018stimulus modality\u2019 dimension. The three independent feature-coding dimensions together specify many parallel VSN pathways in a combinatorial manner and facilitate the complex projection of VSNs in the brainstem. Our study highlights a multidimensional coding architecture of the mammalian vagal interoceptive system for effective signal communication.\n                  <\/jats:p>","DOI":"10.1038\/s41586-022-04515-5","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T13:04:43Z","timestamp":1647435883000},"page":"878-884","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":256,"title":["A multidimensional coding architecture of the vagal interoceptive system"],"prefix":"10.1038","volume":"603","author":[{"given":"Qiancheng","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuyue D.","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian J.","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5282-0682","authenticated-orcid":false,"given":"Rafael","family":"Dai Pra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6953-2943","authenticated-orcid":false,"given":"Rui B.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"4515_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.tins.2020.10.007","volume":"44","author":"WG Chen","year":"2021","unstructured":"Chen, W. 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