Synchronous activation of striatal cholinergic interneurons induces local serotonin release

preprint OA: closed
Full text JSON View at publisher
Full text 12,180 characters · extracted from preprint-html · click to expand
Synchronous activation of striatal cholinergic interneurons induces local serotonin release | 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 Synchronous activation of striatal cholinergic interneurons induces local serotonin release Lior Matityahu, Zachary B. Hobel, Noa Berkowitz, Jeffrey M. Malgady, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5619059/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Mar, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Striatal cholinergic interneurons (CINs) activate nicotinic acetylcholine receptors on dopamine axons to extend the range of dopamine release. Here we show that synchronous activation of CINs induces and extends the range of local serotonin release via a similar mechanism. This process is exaggerated in the hypercholinergic striatum of a mouse model of OCD-like behavior, implicating CINs as critical regulators of serotonin levels in the healthy and pathological striatum. Biological sciences/Neuroscience/Neural circuits Biological sciences/Neuroscience/Synaptic transmission/Neurotransmitters Health sciences/Diseases/Psychiatric disorders/Obsessive compulsive disorder Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 16 Mar, 2026 Read the published version in Nature Communications → 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5619059","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":392768236,"identity":"a3e89a75-0750-4cb0-994e-07f49b54af29","order_by":0,"name":"Lior Matityahu","email":"","orcid":"https://orcid.org/0000-0002-6115-8608","institution":"Department of Medical Neurobiology, Institute of Medical Research Israel – Canada, Faculty of the Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112102, Israel","correspondingAuthor":false,"prefix":"","firstName":"Lior","middleName":"","lastName":"Matityahu","suffix":""},{"id":392768237,"identity":"27d0a49e-771b-4ecb-8f11-6d6f3f13e9b1","order_by":1,"name":"Zachary B. Hobel","email":"","orcid":"https://orcid.org/0000-0002-8229-027X","institution":"Department of Neurobiology and Behavior, Center for Nervous System Disorders, Stony Brook University Renaissance School of Medicine, Stony Brook University, Stony Brook, New York, 11794, USA","correspondingAuthor":false,"prefix":"","firstName":"Zachary","middleName":"B.","lastName":"Hobel","suffix":""},{"id":392768238,"identity":"1374bea8-60fa-497e-a514-52f189f271f8","order_by":2,"name":"Noa Berkowitz","email":"","orcid":"","institution":"Department of Medical Neurobiology, Institute of Medical Research Israel – Canada, Faculty of the Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112102, Israel","correspondingAuthor":false,"prefix":"","firstName":"Noa","middleName":"","lastName":"Berkowitz","suffix":""},{"id":392768239,"identity":"b6e9aa35-3886-4316-a6be-211254b4c666","order_by":3,"name":"Jeffrey M. Malgady","email":"","orcid":"https://orcid.org/0000-0002-1129-2155","institution":"Department of Neurobiology and Behavior, Center for Nervous System Disorders, Stony Brook University Renaissance School of Medicine, Stony Brook University, Stony Brook, New York, 11794, USA","correspondingAuthor":false,"prefix":"","firstName":"Jeffrey","middleName":"M.","lastName":"Malgady","suffix":""},{"id":392768240,"identity":"09b30a36-ba6e-4fca-ac91-c29caf9b0562","order_by":4,"name":"Naomi Gilin","email":"","orcid":"https://orcid.org/0000-0003-0638-532X","institution":"Department of Medical Neurobiology, Institute of Medical Research Israel – Canada, Faculty of the Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112102, Israel","correspondingAuthor":false,"prefix":"","firstName":"Naomi","middleName":"","lastName":"Gilin","suffix":""},{"id":392768241,"identity":"4dec2488-5e3d-45a3-b2d8-a34d0def9bfb","order_by":5,"name":"Joshua L. Plotkin","email":"","orcid":"https://orcid.org/0000-0001-6232-7613","institution":"Department of Neurobiology and Behavior, Center for Nervous System Disorders, Stony Brook University Renaissance School of Medicine, Stony Brook University, Stony Brook, New York, 11794, USA","correspondingAuthor":false,"prefix":"","firstName":"Joshua","middleName":"L.","lastName":"Plotkin","suffix":""},{"id":392768235,"identity":"32f633da-275a-4097-8aa8-06342fbaccc7","order_by":6,"name":"Joshua A. Goldberg","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-5740-4087","institution":"Department of Medical Neurobiology, Institute of Medical Research Israel – Canada, Faculty of the Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112102, Israel","correspondingAuthor":true,"prefix":"","firstName":"Joshua","middleName":"A.","lastName":"Goldberg","suffix":""}],"badges":[],"createdAt":"2024-12-10 18:55:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5619059/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5619059/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41467-026-70359-6","type":"published","date":"2026-03-16T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":104777772,"identity":"023a84ba-9be9-4979-a42b-ec01d8df135d","added_by":"auto","created_at":"2026-03-17 07:12:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1160575,"visible":true,"origin":"","legend":"","description":"","filename":"CIN5HT4NatCommsFinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5619059/v1_covered_542ad894-b7aa-4549-b794-817622dc2511.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Synchronous activation of striatal cholinergic interneurons induces local serotonin release","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"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-5619059/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5619059/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Striatal cholinergic interneurons (CINs) activate nicotinic acetylcholine receptors on dopamine axons to extend the range of dopamine release. Here we show that synchronous activation of CINs induces and extends the range of local serotonin release via a similar mechanism. This process is exaggerated in the hypercholinergic striatum of a mouse model of OCD-like behavior, implicating CINs as critical regulators of serotonin levels in the healthy and pathological striatum.","manuscriptTitle":"Synchronous activation of striatal cholinergic interneurons induces local serotonin release","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-23 05:31:50","doi":"10.21203/rs.3.rs-5619059/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d8d088d1-d662-45e4-bad4-7e0588da2f52","owner":[],"postedDate":"December 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":41872592,"name":"Biological sciences/Neuroscience/Neural circuits"},{"id":41872593,"name":"Biological sciences/Neuroscience/Synaptic transmission/Neurotransmitters"},{"id":41872594,"name":"Health sciences/Diseases/Psychiatric disorders/Obsessive compulsive disorder"}],"tags":[],"updatedAt":"2026-03-17T07:11:50+00:00","versionOfRecord":{"articleIdentity":"rs-5619059","link":"https://doi.org/10.1038/s41467-026-70359-6","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2026-03-16 04:00:00","publishedOnDateReadable":"March 16th, 2026"},"versionCreatedAt":"2024-12-23 05:31:50","video":"","vorDoi":"10.1038/s41467-026-70359-6","vorDoiUrl":"https://doi.org/10.1038/s41467-026-70359-6","workflowStages":[]},"version":"v1","identity":"rs-5619059","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5619059","identity":"rs-5619059","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2024) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00