{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:46:48Z","timestamp":1793407608052,"version":"4.5.0"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"47","license":[{"start":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T00:00:00Z","timestamp":1604880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH\/NIGMS","award":["1R01GM132672-01"],"award-info":[{"award-number":["1R01GM132672-01"]}]},{"name":"NIH\/NIGMS","award":["1R35GM118182-01"],"award-info":[{"award-number":["1R35GM118182-01"]}]},{"name":"NIH\/NIGMS","award":["1R01GM128008-01"],"award-info":[{"award-number":["1R01GM128008-01"]}]},{"name":"NIH\/NIAID","award":["1P01AI102852-01A1"],"award-info":[{"award-number":["1P01AI102852-01A1"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,11,24]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Electronic devices that stimulate electrical activity in the vagus nerve are being studied for clinical use in rheumatoid arthritis, inflammatory bowel disease, and other inflammatory syndromes because vagus nerve signals inhibit inflammation and cytokine production. A vagus nerve mechanism, termed the inflammatory reflex, has been widely studied, but the origin and functional neuroanatomy of vagus nerve fibers controlling inflammation were previously unknown. Here we reveal cholinergic neurons in the brainstem dorsal motor nucleus (DMN) of the vagus projecting to the celiac-superior mesenteric ganglia and transmitting cytokine-inhibiting signals to the splenic nerve. By combining optogenetics, anatomical and functional mapping, and measurement of TNF production, our data show the DMN is an important brainstem locus controlling anti-inflammatory signals in the inflammatory reflex.<\/jats:p>","DOI":"10.1073\/pnas.2008213117","type":"journal-article","created":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T20:32:28Z","timestamp":1604953948000},"page":"29803-29810","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":138,"title":["Identification of a brainstem locus that inhibits tumor necrosis factor"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1082-5877","authenticated-orcid":false,"given":"Adam M.","family":"Kressel","sequence":"first","affiliation":[{"name":"Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030;"},{"name":"The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY 11030;"},{"name":"Department of Surgery, North Shore University Hospital, Northwell Health, Manhasset, NY 11030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tea","family":"Tsaava","sequence":"additional","affiliation":[{"name":"Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3313-6858","authenticated-orcid":false,"given":"Yaakov A.","family":"Levine","sequence":"additional","affiliation":[{"name":"Setpoint Medical, Valencia, CA 91355;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5592-4276","authenticated-orcid":false,"given":"Eric H.","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan E.","family":"Addorisio","sequence":"additional","affiliation":[{"name":"Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Burbach","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5016-3161","authenticated-orcid":false,"given":"Daniela","family":"Carnevale","sequence":"additional","affiliation":[{"name":"Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, IS, Italy;"},{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3510-223X","authenticated-orcid":false,"given":"Giuseppe","family":"Lembo","sequence":"additional","affiliation":[{"name":"Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, IS, Italy;"},{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony M.","family":"Zador","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0316-3860","authenticated-orcid":false,"given":"Ulf","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Karolinska Institute, Karolinska University Hospital, 17176 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1994-2853","authenticated-orcid":false,"given":"Valentin A.","family":"Pavlov","sequence":"additional","affiliation":[{"name":"Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030;"},{"name":"The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY 11030;"},{"name":"Department of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell Health, Hempstead, NY 11549"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4822-3356","authenticated-orcid":false,"given":"Sangeeta S.","family":"Chavan","sequence":"additional","affiliation":[{"name":"Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030;"},{"name":"The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY 11030;"},{"name":"Department of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell Health, Hempstead, NY 11549"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Tracey","sequence":"additional","affiliation":[{"name":"Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030;"},{"name":"The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY 11030;"},{"name":"Department of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell Health, Hempstead, NY 11549"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,11,9]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"R13","article-title":"Localization of efferent function in the dorsal motor nucleus of the vagus","volume":"252","author":"Laughton W. B.","year":"1987","unstructured":"W. B. Laughton, T. L. Powley, Localization of efferent function in the dorsal motor nucleus of the vagus. Am. J. Physiol. 252, R13\u2013R25 (1987).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.68.040504.094635"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-112-3-904"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.46.5.606"},{"key":"e_1_3_4_5_2","first-page":"1189","article-title":"Behavioral stress and tumor progression","volume":"26","author":"Montgomery J. P.","year":"2006","unstructured":"J. P. Montgomery, P. H. Patterson, Behavioral stress and tumor progression. Anticancer Res. 26, 1189\u20131192 (2006).","journal-title":"Anticancer Res."},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903580309"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00185458"},{"key":"e_1_3_4_8_2","first-page":"R200","article-title":"Topography of efferent vagal innervation of the rat gastrointestinal tract","volume":"260","author":"Berthoud H.-R.","year":"1991","unstructured":"H.-R. Berthoud, N. R. Carlson, T. L. Powley, Topography of efferent vagal innervation of the rat gastrointestinal tract. Am. J. Physiol. 260, R200\u2013R207 (1991).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/163.6.1177"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/330662a0"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3764421"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.3.1211"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/35013070"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01321"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1124"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1229"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.008"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601613"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053158"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14515"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803237105"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0889-1591(89)90028-7"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0889-1591(89)90029-9"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209985"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01339"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000050627.90734.ED"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2013.00117"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1067\/mva.2002.129643"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-0702(00)00233-2"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052362"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104530"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00405"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1605635113"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12792"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(20)30172-7"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1525"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.62051653.x"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.1999.00977.x"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1982.tb01175.x"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02648"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2017.06.019"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.08.188"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.02.011"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(93)90046-W"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0029(19960901)35:1<80::AID-JEMT7>3.0.CO;2-W"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(85)80082-9"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8430330"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1993.tb03313.x"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aef163"},{"key":"e_1_3_4_50_2","first-page":"1114","article-title":"Effects of cholinergic blockade, adrenergic blockade and sympathetic denervation on gastrointestinal myoelectric activity in Guinea pig","volume":"238","author":"Galligan J. J.","year":"1986","unstructured":"J. J. Galligan, J. B. Furness, M. Costa, Effects of cholinergic blockade, adrenergic blockade and sympathetic denervation on gastrointestinal myoelectric activity in Guinea pig. J. Pharmacol. Exp. Ther. 238, 1114\u20131125 (1986).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.5.3535"},{"key":"e_1_3_4_52_2","volume-title":"Ueber die Textur der Medulla oblongata","author":"Stilling B.","year":"1843","unstructured":"B. Stilling, Ueber die Textur der Medulla oblongata (Erlangen F Enke, 1843)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2008213117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2008213117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T07:13:16Z","timestamp":1649833996000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2008213117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,9]]},"references-count":52,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2020,11,24]]}},"alternative-id":["10.1073\/pnas.2008213117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2008213117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,9]]},"assertion":[{"value":"2020-11-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}