{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:27:31Z","timestamp":1789000051390,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01 HL133360"],"award-info":[{"award-number":["U01 HL133360"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL161696"],"award-info":[{"award-number":["R01 HL161696"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OT2 OD030534"],"award-info":[{"award-number":["OT2 OD030534"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1940700"],"award-info":[{"award-number":["1940700"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The vagus nerve is a key mediator of brain\u2013heart signaling, and its activity is necessary for cardiovascular health. Vagal outflow stems from the nucleus ambiguus, responsible primarily for fast, beat\u2010to\u2010beat regulation of heart rate and rhythm, and the dorsal motor nucleus of the vagus, responsible primarily for slow regulation of ventricular contractility. Due to the high\u2010dimensional and multimodal nature of the anatomical, molecular and physiological data on neural regulation of cardiac function, data\u2010derived mechanistic insights have proven elusive. Elucidating insights has been complicated further by the broad distribution of the data across heart, brain and peripheral nervous system circuits. Here we lay out an integrative framework based on computational modelling for combining these disparate and multi\u2010scale data on the two vagal control lanes of the cardiovascular system. Newly available molecular\u2010scale data, particularly single\u2010cell transcriptomic analyses, have augmented our understanding of the heterogeneous neuronal states underlying vagally mediated fast and slow regulation of cardiac physiology. Cellular\u2010scale computational models built from these data sets represent building blocks that can be combined using anatomical and neural circuit connectivity, neuronal electrophysiology, and organ\/organismal\u2010scale physiology data to create multi\u2010system, multi\u2010scale models that enable in silico exploration of the fast versus slow lane vagal stimulation. The insights from the computational modelling and analyses will guide new experimental questions on the mechanisms regulating the fast and slow lanes of the cardiac vagus toward exploiting targeted vagal neuromodulatory activity to promote cardiovascular health.<\/jats:p>","DOI":"10.1113\/ep090865","type":"journal-article","created":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T16:13:35Z","timestamp":1682871215000},"page":"1994-2000","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Unpacking the multimodal, multi\u2010scale data of the fast and slow lanes of the cardiac vagus through computational modelling"],"prefix":"10.1113","volume":"109","author":[{"given":"Michelle M.","family":"Gee","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering University of Delaware  Newark Delaware USA"},{"name":"Department of Pathology and Genomic Medicine Daniel Baugh Institute of Functional Genomics\/Computational Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eden","family":"Hornung","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine Daniel Baugh Institute of Functional Genomics\/Computational Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1155-1791","authenticated-orcid":false,"given":"Suranjana","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology SUNY Downstate Health Sciences University  Brooklyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J. H.","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology SUNY Downstate Health Sciences University  Brooklyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixi (Jack)","family":"Cheng","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine University of Central Florida  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Lytton","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology SUNY Downstate Health Sciences University  Brooklyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham M.","family":"Lenhoff","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering University of Delaware  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Schwaber","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine Daniel Baugh Institute of Functional Genomics\/Computational Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8405-1037","authenticated-orcid":false,"given":"Rajanikanth","family":"Vadigepalli","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine Daniel Baugh Institute of Functional Genomics\/Computational Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274678"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2007.041178"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay8086"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00286.2017"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00143.2003"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.257758"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.06.036"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02540-4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273164"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/aic.18033"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102143"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2016.06.003"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2022.36.S1.R4416"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.617459"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180194"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurom.2022.01.008"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.04.096"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs212"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.214320"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102713"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.693735"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.161802.113"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00470"},{"key":"e_1_2_8_25_1","volume-title":"Functional recordings from the pig intrinsic cardiac nervous system (ICN)","author":"Rajendran P.","year":"2019"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(99)00242-7"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","unstructured":"Ursino M. &Magosso E.(2006).Short\u2010term autonomic control of the cardio\u2010respiratory system: A summary with the help of a comprehensive mathematical model.Annual International Conference of the IEEE Engineering in Medicine and Biology Society 2006 354\u2013358.","DOI":"10.1109\/IEMBS.2006.259297"},{"key":"e_1_2_8_28_1","volume-title":"Neuromodulatory networks of the fast and slow lanes of the cardiac vagus","author":"Vadigepalli R.","year":"2022"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1162\/089976601750541796"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2020.01.011"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00279.2014"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04515-5"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP090865","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP090865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T11:02:06Z","timestamp":1732964526000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP090865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,30]]},"references-count":31,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1113\/EP090865"],"URL":"https:\/\/doi.org\/10.1113\/ep090865","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,30]]},"assertion":[{"value":"2023-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}