Deep brain stimulation alleviates Parkinsonian motor deficits through desynchronizing GABA release

Deep brain stimulation alleviates Parkinsonian motor deficits through desynchronizing GABA 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 Deep brain stimulation alleviates Parkinsonian motor deficits through desynchronizing GABA release Yousheng Shu, Zongyi Xu, Wei Duan, Shuyu Yuan, Xiaoxue Zhang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5047146/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Apr, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract High-frequency deep brain stimulation (DBS) of subthalamic nucleus (STN) is an effective clinical therapy for Parkinson's disease (PD), but the underlying cellular and circuit mechanism remains unclear. Here we find a critical role of asynchronous release (AR) of GABA induced by high-frequency stimulation (HFS) at STN in the improvement of motor functions in dopamine-depleted (DD) mice. HFS at 130 Hz causes an initial inhibition followed by desynchronization of spiking activity of STN neurons, largely attributable to presynaptic GABA release. In contrast, low-frequency stimulation (LFS) at 20 Hz produces much weaker AR and a neglectable effect on spiking activity of STN neurons. Further experiments demonstrate that the activation of parvalbumin (PV) axons, but not non-PV axons, from external globus pallidus (GPe) is both necessary and sufficient for the therapeutic effect of DBS. A decrease in AR strength diminishes the high-frequency DBS effect, whereas an increase in AR strength enhances the effect of low-frequency DBS. Together, our results reveal a crucial role of asynchronous GABA release from GPe PV neurons in the improvement of motor functions under Parkinsonian conditions. Biological sciences/Neuroscience/Diseases of the nervous system/Parkinson's disease Biological sciences/Neuroscience/Motor control/Basal ganglia Full Text Additional Declarations There is NO Competing Interest. All experiments and procedures were approved by the Institutional Animal Care and Use Committee of the Department of Laboratory Animal Science at Fudan University. Supplementary Files SupplementarytableStatisticsandnnumbers.pdf Supplementary table of statistics and n numbers Supplementaryvideo1OptogeneticactivationofPVaxons.mp4 Supplementary video1: Optogenetic activation of PV axons Supplementaryvideo2DBSeffectofmicewithPVcellablation.mp4 Supplementary video2: DBS effect in DD mice with ablation of GPe-PV cells Supplementaryvideo3OptogeneticstimulationofSyt1KDPVaxons.mp4 Supplementary video3: Optogenetic stimulation of PV axons with Syt1 downregulation Cite Share Download PDF Status: Published Journal Publication published 19 Apr, 2025 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. 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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-5047146","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":354766947,"identity":"87c44f12-2a9b-4850-987c-6a65b466afa6","order_by":0,"name":"Yousheng 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