Sensitive dLight for imaging broad-spectrum dopamine events across brain regions

Sensitive dLight for imaging broad-spectrum dopamine events across brain regions | 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 Biological Sciences - Article Sensitive dLight for imaging broad-spectrum dopamine events across brain regions Lin Tian, Jacob Roshgadol, Julie Chouinard, Shouvik Majumder, and 33 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7313638/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Dopaminergic neurons modulate movement, motivation, and learning by dynamically regulating dopamine release across distributed neural circuits. However, existing genetically encoded dopamine sensors lack the sensitivity and resolution to capture the full amplitude and temporal complexity of in vivo dopamine signaling, limiting insight into its functions across behavioral contexts. Here, we present dLight3.8, a fluorescence-intensity and lifetime-based sensor with a substantially expanded dynamic range compared to existing dopamine sensors, enabling transformative detection and differentiation of dopamine release across brain regions and behaviors. Specifically, the enhanced sensitivity of dLight3.8 permits robust, single-trial recording of dopamine release spanning a wide concentration range in response to electrical, optogenetic, and behavioral stimuli, in multiple species and circuits. Using dLight3.8, we uncover a region-specific, gradual shift in dopamine encoding across motor learning, from tracking lick timing to signaling reward prediction. Our findings demonstrate that dLigth3.8 provides quantitatively reliable, highly sensitive measurements of graded dopamine release, which is essential for elucidating diverse roles of dopamine signaling in shaping animal behavior. Biological sciences/Biological techniques/Optogenetics Biological sciences/Biotechnology/Molecular engineering/Protein design Biological sciences/Neuroscience/Reward Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryFigures.pdf Supplementary Figures 1-2 SupplementaryTable1.xlsx Supplementary Table 1 SupplementaryTable2.xlsx Supplementary Table 2 SupplementaryTable3.xlsx Supplementary Table 3 SupplementaryTable4.xlsx Supplementary Table 4 SupplementaryTable5.xlsx Supplementary Table 5 SupplementaryTable6.xlsx Supplementary Table 6 ExtendedDataFigure1final.pdf Extended Data 1 ExtendedDataFigure2final.pdf Extended Data 2 ExtendedDataFigure3final.pdf Extended Data 3 ExtendedDataFigure4final.pdf Extended Data 4 ExtendedDataFigure5final.pdf Extended Data 5 ExtendedDataFigure6final.pdf Extended Data 6 ExtendedDataFigure7final.pdf Extended Data 7 ExtendedDataFigure8final.pdf Extended Data 8 ExtendedDataFigure9final.pdf Extended Data 9 ExtendedDataFigure10final.pdf Extended Data 10 Cite Share Download PDF Status: Posted 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-7313638","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":502206208,"identity":"de04d384-407e-44f9-9b52-f91da70d9094","order_by":0,"name":"Lin 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