{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T07:57:37Z","timestamp":1768118257588,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470573"],"award-info":[{"award-number":["82470573"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008868","name":"Jiangsu Provincial Department of Science and Technology","doi-asserted-by":"crossref","award":["BE2023710"],"award-info":[{"award-number":["BE2023710"]}],"id":[{"id":"10.13039\/501100008868","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"crossref","award":["BK20250362"],"award-info":[{"award-number":["BK20250362"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"crossref"}]},{"name":"First Affiliated Hospital of Soochow University","award":["2024006902017"],"award-info":[{"award-number":["2024006902017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic disorder of gut\u2013brain interaction characterized by intestinal dysmotility. Central sensitization has a proposed role in intestinal dysmotility, yet the precise neural circuits and mechanisms remain poorly understood. In this study, we established a neonatal maternal deprivation plus restraint stress (NMD + RS) mouse model that recapitulates key diarrhea-like phenotypes. Neural activation mapping revealed a significant upregulation of c-Fos expression within the medial prefrontal cortex (mPFC) and locus coeruleus (LC), which was predominantly localized to glutamatergic neurons. Chemogenetic inhibition of mPFC glutamatergic neurons suppressed intestinal dysmotility, whereas the activation of mPFC glutamatergic neurons evoked intestinal dysmotility in control mice. Furthermore, viral tracing revealed direct projections from mPFC neurons to glutamatergic neurons in the LC. Subsequent chemogenetic manipulation of these LC glutamatergic neurons receiving projection from mPFC neurons similarly regulated intestinal motility, demonstrating a functional downstream node. Critically, selective activation of the mPFC-LC glutamatergic circuit significantly induced intestinal dysmotility in CON mice. In contrast, inhibition of the mPFC-LC glutamatergic circuit significantly ameliorated intestinal dysmotility in NMD + RS mice. Our findings proved that the enhanced activity of the mPFC-LC circuit led to intestinal dysmotility in NMD + RS mice, hopefully providing new mechanistic perspectives and a potential neuromodulatory target for clinical management of IBS.<\/jats:p>","DOI":"10.3390\/ijms27020681","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:52:17Z","timestamp":1767963137000},"page":"681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Glutamatergic Medial Prefrontal Cortex\u2013Locus Coeruleus Circuit Drives Intestinal Dysmotility in Diarrhea-Predominant Irritable Bowel Syndrome"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6487-545X","authenticated-orcid":false,"given":"Shu-Man","family":"Jia","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai-Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Fen","family":"Hu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui-Xia","family":"Weng","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-6317","authenticated-orcid":false,"given":"Qian","family":"Sun","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Altomare, A., Di Rosa, C., Imperia, E., Emerenziani, S., Cicala, M., and Guarino, M.P.L. 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