{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:49:26Z","timestamp":1787010566841,"version":"build-2736575974"},"posted":{"date-parts":[[2023,7,1]]},"group-title":"Neuroscience","reference-count":85,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,7,1]]},"abstract":"<jats:p>\n                  Interoception broadly refers to awareness of one\u2019s internal milieu. Vagal sensory afferents monitor the internal milieu and maintain homeostasis by engaging brain circuits that alter physiology and behavior. While the importance of the body-to-brain communication that underlies interoception is implicit, the vagal afferents and corresponding brain circuits that shape perception of the viscera are largely unknown. Here, we use mice to parse neural circuits subserving interoception of the heart and gut. We determine vagal sensory afferents expressing the oxytocin receptor, hereafter referred to as NDG\n                  <jats:sup>Oxtr<\/jats:sup>\n                  , send projections to the aortic arch or stomach and duodenum with molecular and structural features indicative of mechanosensation. Chemogenetic excitation of NDG\n                  <jats:sup>Oxtr<\/jats:sup>\n                  significantly decreases food and water consumption, and remarkably, produces a torpor-like phenotype characterized by reductions in cardiac output, body temperature, and energy expenditure. Chemogenetic excitation of NDG\n                  <jats:sup>Oxtr<\/jats:sup>\n                  also creates patterns of brain activity associated with augmented hypothalamic-pituitary-adrenal axis activity and behavioral indices of vigilance. Recurrent excitation of NDG\n                  <jats:sup>Oxtr<\/jats:sup>\n                  suppresses food intake and lowers body mass, indicating that mechanosensation of the heart and gut can exert enduring effects on energy balance. These findings suggest that the sensation of vascular stretch and gastrointestinal distention may have profound effects on whole body metabolism and mental health.\n                <\/jats:p>","DOI":"10.1101\/2023.06.29.547073","type":"posted-content","created":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T21:30:12Z","timestamp":1688247012000},"source":"Crossref","is-referenced-by-count":3,"title":["Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice"],"prefix":"10.64898","author":[{"given":"Karen A.","family":"Scott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0786-7865","authenticated-orcid":false,"given":"Yalun","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique N.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9581-918X","authenticated-orcid":false,"given":"Khalid","family":"Elsaafien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6287-5887","authenticated-orcid":false,"given":"Caitlin","family":"Baumer-Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia A.","family":"Eikenberry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Sa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0032-8810","authenticated-orcid":false,"given":"Guillaume","family":"de Lartigue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7213-6957","authenticated-orcid":false,"given":"Annette D.","family":"de Kloet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-3113","authenticated-orcid":false,"given":"Eric G.","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023070614300869000_2023.06.29.547073v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.09.011"},{"key":"2023070614300869000_2023.06.29.547073v1.2","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/s41586-023-05748-8","article-title":"Cardiogenic control of affective behavioural state","volume":"615","year":"2023","journal-title":"Nature"},{"key":"2023070614300869000_2023.06.29.547073v1.3","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.biopsych.2022.04.020","article-title":"Neural Pathway for Gut Feelings: Vagal Interoceptive Feedback From the Gastrointestinal Tract Is a Critical Modulator of Anxiety-like Behavior","volume":"92","year":"2022","journal-title":"Biol Psychiatry"},{"key":"2023070614300869000_2023.06.29.547073v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04639-1"},{"key":"2023070614300869000_2023.06.29.547073v1.5","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.841078"},{"key":"2023070614300869000_2023.06.29.547073v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.049"},{"key":"2023070614300869000_2023.06.29.547073v1.7","doi-asserted-by":"publisher","DOI":"10.1006\/frne.1993.1010"},{"key":"2023070614300869000_2023.06.29.547073v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.09.008"},{"key":"2023070614300869000_2023.06.29.547073v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.04.096"},{"key":"2023070614300869000_2023.06.29.547073v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.031"},{"key":"2023070614300869000_2023.06.29.547073v1.11","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2017"},{"key":"2023070614300869000_2023.06.29.547073v1.12","doi-asserted-by":"crossref","unstructured":"Ambler, M. , Hitrec, T. & Pickering, A . Turn it off and on again: characteristics and control of torpor [version 2; peer review: 2 approved, 1 approved with reservations, 1 not approved]. Wellcome Open Research 6 (2022). https:\/\/doi.org:10.12688\/wellcomeopenres.17379.2","DOI":"10.12688\/wellcomeopenres.17379.2"},{"key":"2023070614300869000_2023.06.29.547073v1.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2944-18.2019"},{"key":"2023070614300869000_2023.06.29.547073v1.14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00344.2014"},{"key":"2023070614300869000_2023.06.29.547073v1.15","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20001218)428:3<558::AID-CNE11>3.0.CO;2-M"},{"key":"2023070614300869000_2023.06.29.547073v1.16","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(20000605)421:3<302::AID-CNE2>3.0.CO;2-N"},{"key":"2023070614300869000_2023.06.29.547073v1.17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1566-0702(00)00215-0","article-title":"Functional and chemical anatomy of the afferent vagal system","volume":"85","year":"2000","journal-title":"Autonomic Neuroscience-Basic & Clinical"},{"key":"2023070614300869000_2023.06.29.547073v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.011"},{"key":"2023070614300869000_2023.06.29.547073v1.19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00255.x"},{"key":"2023070614300869000_2023.06.29.547073v1.20","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1016\/j.celrep.2019.10.040","article-title":"Arterial Baroreceptors Sense Blood Pressure through Decorated Aortic Claws","volume":"29","year":"2019","journal-title":"Cell Reports"},{"key":"2023070614300869000_2023.06.29.547073v1.21","first-page":"3052","article-title":"The molecular makeup of peripheral and central baroreceptors: stretching a role for Transient Receptor Potential (TRP), Epithelial Sodium Channel (ENaC), Acid Sensing Ion Channel (ASIC), and Piezo channels","volume":"118","year":"2021","journal-title":"Cardiovascular research"},{"key":"2023070614300869000_2023.06.29.547073v1.22","first-page":"R766","article-title":"Gastric volume rather than nutrient content inhibits food intake","volume":"271","year":"1996","journal-title":"Am J Physiol"},{"key":"2023070614300869000_2023.06.29.547073v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(85)90214-8"},{"key":"2023070614300869000_2023.06.29.547073v1.24","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.soard.2019.10.011","article-title":"Changes in resting metabolic rate and body composition due to intragastric balloon therapy","volume":"16","year":"2020","journal-title":"Surg Obes Relat Dis"},{"key":"2023070614300869000_2023.06.29.547073v1.25","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/oby.22138","article-title":"Resting Metabolic Rate, Total Daily Energy Expenditure, and Metabolic Adaptation 6 Months and 24 Months After Bariatric Surgery","volume":"26","year":"2018","journal-title":"Obesity (Silver Spring)"},{"key":"2023070614300869000_2023.06.29.547073v1.26","doi-asserted-by":"crossref","first-page":"R214","DOI":"10.1152\/ajpregu.2001.280.1.R214","article-title":"Acute hypertension inhibits thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats","volume":"280","year":"2001","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2023070614300869000_2023.06.29.547073v1.27","first-page":"542","article-title":"The role of the heart in body fluid and electrolyte homeostasis","volume":"79","year":"1984","journal-title":"J Physiol (Paris)"},{"key":"2023070614300869000_2023.06.29.547073v1.28","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1984.sp015162"},{"key":"2023070614300869000_2023.06.29.547073v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.06.015"},{"key":"2023070614300869000_2023.06.29.547073v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.07.013"},{"key":"2023070614300869000_2023.06.29.547073v1.31","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/dom.14843","article-title":"Tirzepatide suppresses palatable food intake by selectively reducing preference for fat in rodents","volume":"25","year":"2023","journal-title":"Diabetes Obes Metab"},{"key":"2023070614300869000_2023.06.29.547073v1.32","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/s42255-021-00363-1","article-title":"A genetic map of the mouse dorsal vagal complex and its role in obesity","volume":"3","year":"2021","journal-title":"Nat Metab"},{"key":"2023070614300869000_2023.06.29.547073v1.33","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.neuron.2020.11.010","article-title":"Area Postrema Cell Types that Mediate Nausea-Associated Behaviors","volume":"109","year":"2021","journal-title":"Neuron"},{"key":"2023070614300869000_2023.06.29.547073v1.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1162-19.2019"},{"key":"2023070614300869000_2023.06.29.547073v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/nature25511"},{"key":"2023070614300869000_2023.06.29.547073v1.36","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.neuron.2018.09.032","article-title":"Parabrachial CGRP Neurons Establish and Sustain Aversive Taste Memories","volume":"100","year":"2018","journal-title":"Neuron"},{"key":"2023070614300869000_2023.06.29.547073v1.37","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3674-16.2017"},{"key":"2023070614300869000_2023.06.29.547073v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0591-0"},{"key":"2023070614300869000_2023.06.29.547073v1.39","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034133"},{"key":"2023070614300869000_2023.06.29.547073v1.40","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22850"},{"key":"2023070614300869000_2023.06.29.547073v1.41","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/brv.12671","article-title":"Human torpor: translating insights from nature into manned deep space expedition","volume":"96","year":"2021","journal-title":"Biol Rev Camb Philos Soc"},{"key":"2023070614300869000_2023.06.29.547073v1.42","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0642"},{"key":"2023070614300869000_2023.06.29.547073v1.43","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242613"},{"key":"2023070614300869000_2023.06.29.547073v1.44","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-102320-102847"},{"key":"2023070614300869000_2023.06.29.547073v1.45","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-013-1636-4"},{"key":"2023070614300869000_2023.06.29.547073v1.46","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.66.032102.115313"},{"key":"2023070614300869000_2023.06.29.547073v1.47","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.56.030194.000521"},{"key":"2023070614300869000_2023.06.29.547073v1.48","first-page":"H1307","article-title":"Non-NMDA receptors mediate sensory afferent synaptic transmission in medial nucleus tractus solitarius","volume":"259","year":"1990","journal-title":"Am J Physiol"},{"key":"2023070614300869000_2023.06.29.547073v1.49","first-page":"H1674","article-title":"Area postrema and aortic or vagal afferents converge to excite cells in nucleus tractus solitarius","volume":"264","year":"1993","journal-title":"Am J Physiol"},{"key":"2023070614300869000_2023.06.29.547073v1.50","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00315.2019"},{"key":"2023070614300869000_2023.06.29.547073v1.51","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6324"},{"key":"2023070614300869000_2023.06.29.547073v1.52","first-page":"R354","article-title":"Hemodynamic, hormonal, and drinking responses to reduced venous return in the dog","volume":"243","year":"1982","journal-title":"Am J Physiol"},{"key":"2023070614300869000_2023.06.29.547073v1.53","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00651.2001"},{"key":"2023070614300869000_2023.06.29.547073v1.54","first-page":"103P","article-title":"Vagal mechanoreceptors of the lower oesophageal sphincter and of the pyloric sphincter in the cat","volume":"245","year":"1975","journal-title":"The Journal of physiology"},{"key":"2023070614300869000_2023.06.29.547073v1.55","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1984.sp015388"},{"key":"2023070614300869000_2023.06.29.547073v1.56","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1957.sp001228"},{"key":"2023070614300869000_2023.06.29.547073v1.57","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1152\/jn.1989.61.5.1001","article-title":"Characteristics of vagal esophageal tension-sensitive afferent fibers in the opossum","volume":"61","year":"1989","journal-title":"J Neurophysiol"},{"key":"2023070614300869000_2023.06.29.547073v1.58","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903190206"},{"key":"2023070614300869000_2023.06.29.547073v1.59","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.051862"},{"key":"2023070614300869000_2023.06.29.547073v1.60","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.080879"},{"key":"2023070614300869000_2023.06.29.547073v1.61","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1016\/j.neuron.2021.04.028","article-title":"Periphery signals generated by Piezo-mediated stomach stretch and Neuromedin-mediated glucose load regulate the Drosophila brain nutrient sensor","volume":"109","year":"2021","journal-title":"Neuron"},{"key":"2023070614300869000_2023.06.29.547073v1.62","doi-asserted-by":"crossref","unstructured":"Min, S. et al. Control of feeding by Piezo-mediated gut mechanosensation in Drosophila. Elife 10 (2021). https:\/\/doi.org:10.7554\/eLife.63049","DOI":"10.7554\/eLife.63049"},{"key":"2023070614300869000_2023.06.29.547073v1.63","doi-asserted-by":"crossref","first-page":"8599","DOI":"10.1038\/s41598-017-09318-7","article-title":"Impact of sex, fat distribution and initial body weight on oxytocin\u2019s body weight regulation","volume":"7","year":"2017","journal-title":"Sci Rep"},{"key":"2023070614300869000_2023.06.29.547073v1.64","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/dom.14937","article-title":"Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects","volume":"25","year":"2023","journal-title":"Diabetes Obes Metab"},{"key":"2023070614300869000_2023.06.29.547073v1.65","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s42255-021-00344-4","article-title":"Central and peripheral GLP-1 systems independently suppress eating","volume":"3","year":"2021","journal-title":"Nat Metab"},{"key":"2023070614300869000_2023.06.29.547073v1.66","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/bph.15576","article-title":"The role of nucleus of the solitary tract glucagon-like peptide-1 and prolactin-releasing peptide neurons in stress: anatomy, physiology and cellular interactions","volume":"179","year":"2022","journal-title":"Br J Pharmacol"},{"key":"2023070614300869000_2023.06.29.547073v1.67","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199602290-00035"},{"key":"2023070614300869000_2023.06.29.547073v1.68","doi-asserted-by":"crossref","first-page":"101024","DOI":"10.1016\/j.molmet.2020.101024","article-title":"PPG neurons in the nucleus of the solitary tract modulate heart rate but do not mediate GLP-1 receptor agonist-induced tachycardia in mice","volume":"39","year":"2020","journal-title":"Mol Metab"},{"key":"2023070614300869000_2023.06.29.547073v1.69","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00081.2012"},{"key":"2023070614300869000_2023.06.29.547073v1.70","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00131.2009"},{"key":"2023070614300869000_2023.06.29.547073v1.71","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1038\/s41467-021-22205-0","article-title":"Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation","volume":"12","year":"2021","journal-title":"Nature Communications"},{"key":"2023070614300869000_2023.06.29.547073v1.72","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s42003-020-01629-2","article-title":"Artificial hibernation\/life-protective state induced by thiazoline-related innate fear odors","volume":"4","year":"2021","journal-title":"Communications Biology"},{"key":"2023070614300869000_2023.06.29.547073v1.73","doi-asserted-by":"crossref","first-page":"20182370","DOI":"10.1098\/rspb.2018.2370","article-title":"Torpor reduces predation risk by compensating for the energetic cost of antipredator foraging behaviours","volume":"285","year":"2018","journal-title":"Proceedings of the Royal Society B: Biological Sciences"},{"key":"2023070614300869000_2023.06.29.547073v1.74","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1016\/j.cub.2019.07.038","article-title":"Osmolyte Depletion and Thirst Suppression Allow Hibernators to Survive for Months without Water","volume":"29","year":"2019","journal-title":"Curr Biol"},{"key":"2023070614300869000_2023.06.29.547073v1.75","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1086\/physzool.52.2.30152564","article-title":"Daily Torpor in the Laboratory Mouse, Mus musculus Var","volume":"52","year":"1979","journal-title":"Albino. Physiological Zoology"},{"key":"2023070614300869000_2023.06.29.547073v1.76","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9629(82)90035-4"},{"key":"2023070614300869000_2023.06.29.547073v1.77","doi-asserted-by":"publisher","DOI":"10.1038\/nature02033"},{"key":"2023070614300869000_2023.06.29.547073v1.78","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2707-07.2007"},{"key":"2023070614300869000_2023.06.29.547073v1.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.06.035"},{"key":"2023070614300869000_2023.06.29.547073v1.80","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.02.003"},{"key":"2023070614300869000_2023.06.29.547073v1.81","first-page":"8.6E.1","article-title":"Conditioned Flavor Aversions: Assessment of Drug-Induced Suppression of Food Intake","volume":"5","year":"1998","journal-title":"Current Protocols in Neuroscience"},{"key":"2023070614300869000_2023.06.29.547073v1.82","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0477"},{"key":"2023070614300869000_2023.06.29.547073v1.83","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1131"},{"key":"2023070614300869000_2023.06.29.547073v1.84","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2023070614300869000_2023.06.29.547073v1.85","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2010.04.011"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.06.29.547073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:52:11Z","timestamp":1768452731000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.06.29.547073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,1]]},"references-count":85,"URL":"https:\/\/doi.org\/10.1101\/2023.06.29.547073","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s42255-024-01205-6","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,7,1]]},"subtype":"preprint"}}