Peptidergic top-down control of metabolic state-dependent behavioral decisions in a conflicting sensory context

Peptidergic top-down control of metabolic state-dependent behavioral decisions in a conflicting sensory context | 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 Peptidergic top-down control of metabolic state-dependent behavioral decisions in a conflicting sensory context Peter Soba, Bibi Nusreen Imambocus, Yushi Yu, Michael Schleyer This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6198660/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Animals make economically beneficial behavioral decisions by integrating the external sensory environment with their internal state. The metabolic state, i.e. hunger, can shift priorities, prompting risk-taking and reducing responses to danger during foraging activities. How behavioral changes are processed in the nervous system to generate flexible responses based on needs and risks remains largely unclear. Here, we demonstrate in Drosophila larvae that the corticotropin releasing hormone (CRH) homolog diuretic hormone 44 (Dh44) and its producing neurons exert metabolic top-down control of behavioral choice in a conflicting sensory context. The metabolic state via Dh44 signaling mediates the transition from avoiding to tolerating aversive light conditions in the presence of food. In vivo imaging of neuropeptide release revealed that Dh44 regulates the acute release Insulin-like peptide 7 (Ilp7) specifically in a conflicting context, thereby inducing light tolerance. Optogenetic activation of specific subsets of Dh44 or Ilp7 producing neurons during starvation is sufficient to shift behavior from light tolerance to avoidance by regulating light avoidance circuit responses. This top-down feedforward peptidergic circuit may represent a general mechanism that helps organisms to balance risk-taking with metabolic needs by allowing flexible adjustment of behavior in a conflicting multisensory environment. Biological sciences/Neuroscience/Sensorimotor processing/Decision Biological sciences/Neuroscience/Neural circuits Biological sciences/Physiology/Neurophysiology Biological sciences/Neuroscience/Sensory processing Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6198660","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":428936036,"identity":"a778c6dd-3e49-4ef9-9129-15026a3c61e8","order_by":0,"name":"Peter Soba","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYDADAwbmAx+ANGMDYbXMMC1siTNI1cJjSJwWc/b+g48rGOrkzNnPfGz42cYg209Ii2XPYWbDMwyHjS17cjc29rYxGM8kZI3BjWQ2yQaGA4kbDuRuf8DbxgBkENJy/zH7zwaGusQN5988bPwL1LKfoJYbzGxAHzMnbriRw9gMtoWwX5KNJRsMgH6Z8cywWeachPEMQraYsx98+LGhAhhi/MkPG9+U2cj2NxByGBIJAhKEnIWseBSMglEwCkYBLgAAdEBCl1hcVAQAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-6163-4686","institution":"University of Erlangen-Nürnberg","correspondingAuthor":true,"prefix":"","firstName":"Peter","middleName":"","lastName":"Soba","suffix":""},{"id":428936037,"identity":"bf2cab1f-c261-4e95-bae4-d4c3a2d2671f","order_by":1,"name":"Bibi Nusreen Imambocus","email":"","orcid":"","institution":"University of Bonn","correspondingAuthor":false,"prefix":"","firstName":"Bibi","middleName":"Nusreen","lastName":"Imambocus","suffix":""},{"id":428936038,"identity":"75e40ea7-0073-4d80-a5e2-2edef19dfaec","order_by":2,"name":"Yushi Yu","email":"","orcid":"","institution":"University of Bonn","correspondingAuthor":false,"prefix":"","firstName":"Yushi","middleName":"","lastName":"Yu","suffix":""},{"id":428936039,"identity":"97d792bd-5c35-4437-9c48-2dd5d7b09730","order_by":3,"name":"Michael Schleyer","email":"","orcid":"","institution":"Hokkaido University","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Schleyer","suffix":""}],"badges":[],"createdAt":"2025-03-10 22:05:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6198660/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6198660/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78720253,"identity":"853a6b5d-6abe-4f89-88b7-32b7a1bb74a5","added_by":"auto","created_at":"2025-03-18 04:23:05","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2571298,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Imambocusetalv8.117417031771.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6198660/v1_covered_1ace5080-5b9d-4f68-86dc-8375e1d1743f.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Peptidergic top-down control of metabolic state-dependent behavioral decisions in a conflicting sensory context","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6198660/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6198660/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Animals make economically beneficial behavioral decisions by integrating the external sensory environment with their internal state. 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