Involvement of the hypothalamus–raphe–spinal defecation center axis in stress-induced defecation in rats

Involvement of the hypothalamus–raphe–spinal defecation center axis in stress-induced defecation in rats | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Involvement of the hypothalamus–raphe–spinal defecation center axis in stress-induced defecation in rats Yasutake Shimizu, Natsufu Yuki, Tomoya Sawamura, Ayuna Mori, Hiroshi Yamaguchi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7144621/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Apr, 2026 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract Stress-induced defecation disorders, such as irritable bowel syndrome (IBS), are widespread. However, the pathophysiology of these disorders remains unclear. While the vagus nerve has been the primary focus of research on the brain‒gut axis, this nerve poorly innervates the distal colon and rectum. Here we provide evidence that the hypothalamus‒raphe‒spinal cord‒pelvic nerve pathway mediates stress-induced defecation in rats. We used viral tracing, pharmacological, and chemogenetic approaches to show that hypothalamic neurons projecting to the raphe nucleus activate descending serotonergic neurons probably via oxytocinergic signaling, thereby stimulating colorectal motility through the pelvic nerves. Inhibiting this pathway suppresses stress-induced defecation. These findings highlight the role of the hypothalamus‒raphe‒spinal defecation center axis in transmitting psychological stress to the colorectum and offer new insights into the pathophysiology of IBS. Biological sciences/Physiology/Neurophysiology Biological sciences/Neuroscience/Stress and resilience Full Text Additional Declarations There is NO Competing Interest. Supplementary Files supplementarystatisticsfile.xlsx Statistical data file SupplementaryFigs.docx Supplemental figures Cite Share Download PDF Status: Published Journal Publication published 01 Apr, 2026 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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