{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T02:44:14Z","timestamp":1776307454293,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>A monosynaptic pathway connects the substantia nigra pars compacta (SNpc) to neurons of the dorsal motor nucleus of the vagus (DMV). This monosynaptic pathway modulates the vagal control of gastric motility. It is not known, however, whether this nigro\u2010vagal pathway also modulates the tone and motility of the proximal colon. In rats, microinjection of retrograde tracers in the proximal colon and of anterograde tracers in SNpc showed that bilaterally labelled colonic\u2010projecting neurons in the DMV received inputs from SNpc neurons. Microinjections of the ionotropic glutamate receptor agonist, NMDA, in the SNpc increased proximal colonic motility and tone, as measured via a strain gauge aligned with the colonic circular smooth muscle; the motility increase was inhibited by acute subdiaphragmatic vagotomy. Upon transfection of SNpc with pAAV\u2010hSyn\u2010hM3D(Gq)\u2010mCherry, chemogenetic activation of nigro\u2010vagal nerve terminals by brainstem application of clozapine\u2010<jats:italic>N<\/jats:italic>\u2010oxide increased the firing rate of DMV neurons and proximal colon motility; both responses were abolished by brainstem pretreatment with the dopaminergic D1\u2010like antagonist SCH23390. Chemogenetic inhibition of nigro\u2010vagal nerve terminals following SNpc transfection with pAAV\u2010hSyn\u2010hM4D(Gi)\u2010mCherry decreased the firing rate of DMV neurons and inhibited proximal colon motility. These data suggest that a nigro\u2010vagal pathway modulates activity of the proximal colon motility tonically via a discrete dopaminergic synapse in a manner dependent on vagal efferent nerve activity. Impairment of this nigro\u2010vagal pathway may contribute to the severely reduced colonic transit and prominent constipation observed in both patients and animal models of parkinsonism.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15756-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Substantia nigra pars compacta (SNpc) neurons are connected to the dorsal motor nucleus of the vagus (DMV) neurons via a presumed direct pathway.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Brainstem neurons in the lateral DMV innervate the proximal colon. Colonic\u2010projecting DMV neurons receive inputs from neurons of the SNpc.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The nigro\u2010vagal pathway modulates tone and motility of the proximal colon via D1\u2010like receptors in the DMV.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present study provides the mechanistic basis for explaining how SNpc alterations may lead to a high rate of constipation in patients with Parkinson's Disease.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284238","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T14:12:01Z","timestamp":1695996721000},"page":"4751-4766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The substantia nigra modulates proximal colon tone and motility in a vagally\u2010dependent manner in the rat"],"prefix":"10.1113","volume":"601","author":[{"given":"Tiaosi","family":"Xing","sequence":"first","affiliation":[{"name":"Department of Neural and Behavioral Sciences Penn State College of Medicine  Hershey PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Nanni","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences Penn State College of Medicine  Hershey PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5062-3703","authenticated-orcid":false,"given":"Cameron R.","family":"Burkholder","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences Penn State College of Medicine  Hershey PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsteen N.","family":"Browning","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences Penn State College of Medicine  Hershey PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-1558","authenticated-orcid":false,"given":"R. Alberto","family":"Travagli","sequence":"additional","affiliation":[{"name":"Neurobiology Research  Newport NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)90419-D"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-018-0066-0"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.08.069"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00180.2017"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00363.2010"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.647555"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1991.260.1.R200"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-179001"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-002-0808-2"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00549.2004"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0521t.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c130055"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.09.030"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6801-2"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27186"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.05.049"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.08.016"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2018.00113"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2017.07.033"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.4.726"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)02937-8"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00007-1"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91066-2"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.32"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.07.024"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12995"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255555"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.165"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.242"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c130026"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.029546"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.060"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2009.08.007"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00112.2019"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2018.09.007"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00923.x"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26866"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12743"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2018.01.010"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2018.11.016"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:DDAS.0000030083.50003.07"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27720"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13633"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100016929"},{"key":"e_1_2_5_47_1","doi-asserted-by":"crossref","unstructured":"Nanni G. &Travagli R. A.(2020).A nigro\u2010vagal pathway controls colonic motility and may be impaired in a model of envoronmental Parkinson's disease. InDigestive Disease Week. Virtual conference.","DOI":"10.1016\/S0016-5085(20)30785-X"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902730206"},{"key":"e_1_2_5_49_1","first-page":"136","article-title":"Gastrointestinal dysfunction in Parkinson's disease","volume":"5","author":"Pfeiffer R. F.","year":"1998","journal-title":"Clinical Neuroscience"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2016.152"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00214.2021"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11938-018-0201-3"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.91"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026648311646"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1787-16.2017"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24448"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.76"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0339-z"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27741"},{"key":"e_1_2_5_61_1","unstructured":"Wood J. D.(1987).Physiology of the enteric nervous system. InL. R.Johnson(Ed.) Physiology of the gatsrointestinal tract(2nd edn pp.67\u2013110).Raven Press."}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP284238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T07:24:50Z","timestamp":1698823490000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP284238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,29]]},"references-count":60,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1113\/JP284238"],"URL":"https:\/\/doi.org\/10.1113\/jp284238","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,29]]},"assertion":[{"value":"2022-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}