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Descending oxytocin (OXT; prototypical anti\u2010stress peptide) and corticotropin releasing factor (CRF; prototypical stress peptide) inputs from the paraventricular nucleus (PVN) of the hypothalamus to the dorsal motor nucleus of the vagus (DMV) modulate the GI stress response. How these descending inputs, and their associated changes to GI motility and stress responses, are altered following pHFD exposure are, however, unknown. The present study used retrograde neuronal tracing experiments, cerebrospinal fluid extraction,\n in vivo<\/jats:italic>\n recordings of gastric tone, motility and gastric emptying rates, and\n in vitro<\/jats:italic>\n electrophysiological recordings from brainstem slice preparations to investigate the hypothesis that pHFD alters descending PVN\u2013DMV inputs and dysregulates vagal brain\u2013gut responses to stress. Compared to controls, rats exposed to pHFD had slower gastric emptying rates and did not respond to acute stress with the expected delay in gastric emptying. Neuronal tracing experiments demonstrated that pHFD reduced the number of PVN\n OXT<\/jats:sup>\n neurons that project to the DMV, but increased PVN\n CRF<\/jats:sup>\n neurons. Both\n in vitro<\/jats:italic>\n electrophysiology recordings of DMV neurons and\n in vivo<\/jats:italic>\n recordings of gastric motility and tone demonstrated that, following pHFD, PVN\n CRF<\/jats:sup>\n \u2013DMV projections were tonically active, and that pharmacological antagonism of brainstem CRF1 receptors restored the appropriate gastric response to brainstem OXT application. These results suggest that pHFD exposure disrupts descending PVN\u2013DMV inputs, leading to a dysregulated vagal brain\u2013gut response to stress.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Maternal high\u2010fat diet exposure is associated with gastric dysregulation and stress sensitivity in offspring.<\/jats:p>\n <\/jats:list-item>\n \n The present study demonstrates that perinatal high\u2010fat diet exposure downregulates hypothalamic\u2013vagal oxytocin (OXT) inputs but upregulates hypothalamic\u2013vagal corticotropin releasing factor (CRF) inputs.<\/jats:p>\n <\/jats:list-item>\n \n \n Both\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n studies demonstrated that, following perinatal high\u2010fat diet, CRF receptors were tonically active at NTS\u2013DMV synapses, and that pharmacological antagonism of these receptors restored the appropriate gastric response to OXT.\n <\/jats:p>\n <\/jats:list-item>\n \n The current study suggests that perinatal high\u2010fat diet exposure disrupts descending PVN\u2013DMV inputs, leading to a dysregulated vagal brain\u2013gut response to stress.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp284726","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T06:43:54Z","timestamp":1683528234000},"page":"2853-2875","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Perinatal high\u2010fat diet exposure alters oxytocin and corticotropin releasing factor inputs onto vagal neurocircuits controlling gastric motility"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-9218","authenticated-orcid":false,"given":"Kaitlin E.","family":"Carson","sequence":"first","affiliation":[{"name":"Department of Neural and Behavioral Sciences Pennsylvania State College of Medicine Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Barrett Honors College Arizona State University Tempe AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine Q.","family":"Mackley","sequence":"additional","affiliation":[{"name":"Schreyer Honors College Pennsylvania State University State College PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Alberto","family":"Travagli","sequence":"additional","affiliation":[{"name":"Neurobiology Research Newport NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5062-3703","authenticated-orcid":false,"given":"Kirsteen N.","family":"Browning","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences Pennsylvania State College of Medicine Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2018.08.003"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0019719"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/dev.21803"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2010.02069.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.282806"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2004.03508.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.0420489"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2004.08.039"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.278192"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c130055"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000449"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2009.04.002"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2009.05.004"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.06-10-02908.1986"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0445"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.106"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1992.03480090092034"},{"issue":"2","key":"e_1_2_5_19_1","article-title":"Effects of oxytocin on attention to emotional faces in healthy volunteers and highly socially anxious males","volume":"18","author":"Clark\u2010Elford R.","year":"2014","journal-title":"The International Journal of Neuropsychopharmacology"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00079.2019"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.139785"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4350"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881111400642"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2018.08.006"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000818"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1992.tb34345.x"},{"key":"e_1_2_5_27_1","first-page":"1","article-title":"Increases in prepregnancy obesity: United States (2016\u20132019)","author":"Driscoll A. 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