Focused Ultrasound Activation of Cultured Primary Sensory Neurons: Molecular and Biophysical Characterization

Focused Ultrasound Activation of Cultured Primary Sensory Neurons: Molecular and Biophysical Characterization | 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 Focused Ultrasound Activation of Cultured Primary Sensory Neurons: Molecular and Biophysical Characterization Elena Brunet, Thibaud Parpaite, Sungae Yoo, Eric Debieu, Khaled Metwally, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6049101/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 Dorsal root ganglion (DRG) neurons have a wide range of functions, including touch, pain and itch. These neurons have recently emerged as promising targets for non-invasive focused ultrasound (FUS) neuromodulation. However, our understanding of the molecular and physical mechanisms underlying FUS-evoked responses in DRG neurons remains limited. Here, we explore the neuromodulatory effects of FUS on cultured DRG neurons using calcium imaging to track neural responses. We find that a 20-MHz FUS burst of 1-ms duration at an acoustic pressure of 5 MPa elicited calcium responses in 52% of DRG neurons. Single-cell RNA sequencing reveals that more than half of FUS-sensitive neurons belong to two subsets: the TH-expressing C low-threshold mechanoreceptors (C-LTMRs) and the MRGPRD-expressing C high-threshold mechanoreceptors (C-HTMRs), both of which express the G αi -interacting protein (GINIP). This finding was further confirmed by using a ginip mouse model. We demonstrate that FUS excites both GINIP+ and GINIP- neurons through membrane deformation, likely mediated by mechanosensitive ion channels. Our findings identify specific FUS parameters that activate distinct subsets of DRG neurons, opening new possibilities for using FUS to modulate DRG neuron activity. Biological sciences/Biotechnology Physical sciences/Nanoscience and technology Full Text Additional Declarations There is NO Competing Interest. All experiments were conducted in line with European guidelines for the care and use of laboratory animals (Council Directive 86/609/EEC). All experimental procedures were approved by an independent ethics committee for animal experimentation (APAFIS), as required by the French law and in accordance with the relevant institutional regulations of French legislation on animal experimentation, under license numbers #30046-2021062313194207 v1 Supplementary Files ExtendedDataTable1.xlsx Supplementary Data Set 1 ExtendedDataTable2.xlsx Supplementary Data Set 2 ExtendedDataTable3.xlsx Supplementary Data Set 3 ExtendedDataTable4.xlsx Supplementary Data Set 4 ExtendedDataTable5.xlsx Supplementary Data Set 5 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-6049101","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":420124319,"identity":"4e8e785b-4c89-45a0-817a-2729ac074074","order_by":0,"name":"Elena Brunet","email":"","orcid":"","institution":"CNRS","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Brunet","suffix":""},{"id":420124320,"identity":"625004f8-622c-48ee-a396-1e38eb323a77","order_by":1,"name":"Thibaud Parpaite","email":"","orcid":"","institution":"UC 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