{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:20:53Z","timestamp":1792729253797,"version":"4.5.0"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP220100070"],"award-info":[{"award-number":["DP220100070"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1156416"],"award-info":[{"award-number":["1156416"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    How the gastrointestinal tract communicates with the brain, via sensory nerves, is of significant interest for our understanding of human health and disease. Enterochromaffin (EC) cells in the gut mucosa release a variety of neurochemicals, including the largest quantity of 5\u2010hydroxytryptamine (5\u2010HT) in the body. How 5\u2010HT and other substances released from EC cells activate sensory nerve endings in the gut wall remains a major unresolved mystery. We used in vivo anterograde tracing from nodose ganglia to determine the spatial relationship between 5\u2010HT synthesizing and peptide\u2010YY (PYY)\u2010synthesizing EC cells and their proximity to vagal afferent nerve endings that project to the mucosa of mouse small intestine. The shortest mean distances between single 5\u2010HT\u2010 and PYY\u2010synthesizing EC cells and the nearest vagal afferent nerve endings in the mucosa were 33.1\u00a0\u00b1\u00a014.4\u00a0\u00b5m (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a056;\n                    <jats:italic>N<\/jats:italic>\n                    \u00a0=\u00a06) and 70.3\u00a0\u00b1\u00a032.3\u00a0\u00b5m (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a016;\n                    <jats:italic>N<\/jats:italic>\n                    \u00a0=\u00a06). No morphological evidence was found to suggest that 5\u2010HT\u2010 or PYY\u2010containing EC cells form close morphological associations with vagal afferents endings, or varicose axons of passage. The large distances between EC cells and vagal afferent endings are many hundreds of times greater than those known to underlie synaptic transmission in the nervous system (typically 10\u201315\u00a0nm). Taken together, the findings lead to the inescapable conclusion that communication between 5\u2010HT\u2010containing EC cells and vagal afferent nerve endings in the mucosa of the mouse small intestinal occurs in a paracrine fashion, via diffusion.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>New and Noteworthy<\/jats:bold>\n                    None of the findings here are consistent with a view that close physical contacts occur between 5\u2010HT\u2010containing EC cells and vagal afferent nerve endings in mouse small intestine. Rather, the findings suggest that gut\u2013brain communication between EC cells and vagal afferent endings occurs via passive diffusion. The morphological data presented do not support the view that EC cells are physically close enough to vagal afferent endings to communicate via fast synaptic transmission.\n                  <\/jats:p>","DOI":"10.1002\/cne.25613","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T12:44:42Z","timestamp":1713271482000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mechanisms underlying the gut\u2013brain communication: How enterochromaffin (EC) cells activate vagal afferent nerve endings in the small intestine"],"prefix":"10.1002","volume":"532","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2190-5303","authenticated-orcid":false,"given":"Nick J.","family":"Spencer","sequence":"first","affiliation":[{"name":"Visceral Neurophysiology Laboratory Flinders Health and Medical Research Institute &amp; College of Medicine and Public Health Flinders University of South Australia  Bedford Park South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda A.","family":"Kyloh","sequence":"additional","affiliation":[{"name":"Visceral Neurophysiology Laboratory Flinders Health and Medical Research Institute &amp; College of Medicine and Public Health Flinders University of South Australia  Bedford Park South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Travis","sequence":"additional","affiliation":[{"name":"Visceral Neurophysiology Laboratory Flinders Health and Medical Research Institute &amp; College of Medicine and Public Health Flinders University of South Australia  Bedford Park South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J","family":"Hibberd","sequence":"additional","affiliation":[{"name":"Visceral Neurophysiology Laboratory Flinders Health and Medical Research Institute &amp; College of Medicine and Public Health Flinders University of South Australia  Bedford Park South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016\u20105085(98)70540\u20102"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.031"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74964"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.034"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903010107"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00185458"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00187819"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000147837"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20108993(96)01222\u2010X"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903190206"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78361"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.05.002"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.29"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025\u20106196(12)62574\u20109"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2018"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00019.2022"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010019\u201003099\u20103"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418\u2010018\u20101746\u2010x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20100897\u20104_3"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.029"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010019\u20100168\u20108"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14966"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2021.110303"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24489"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010019\u201003029\u20103"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079\u20106123(08)62145\u20107"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat5236"},{"key":"e_1_2_8_29_1","volume-title":"Principles of neural science","author":"Kandel E. 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