Solution Manifold in the Electrophysiological Parameter Space of GPe Subtypes: Inverse Leak–HCN Conductance Correlations

Solution Manifold in the Electrophysiological Parameter Space of GPe Subtypes: Inverse Leak–HCN Conductance Correlations | 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 Solution Manifold in the Electrophysiological Parameter Space of GPe Subtypes: Inverse Leak–HCN Conductance Correlations Matheus Sousa, Gabriel Cunha, Gabrielle Tavares, Gilberto Corso, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7471232/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Two primary neuronal subtypes summarize the dynamics of the external segment of the globus pallidus (GPe) with differentanatomical, electrophysiological, and functional properties: prototypical and arkypallidal neurons. Acknowledging these diversesubpopulations has altered comprehension of the GPe, demonstrating its variability and importance in typical and atypical states.In this study, we analyzed, using the Hodgkin-Huxley like model, the dynamics of these two GPe neuron subtypes, scanningconductance values for two ion channels: the leak (gleak) and the HCN (gHCN). We identified, through parameter space gleak vs.gHCN, values of intrinsic electrophysiological responses for each neuronal subtype, such as firing rate, sag-ratio, and troughpotential. With this, we developed a method for intersecting parameter spaces, which finds a subset of electrophysiologicalresults.Finally, from this subset of results, we extracted the linear inverse correlation between gleak and gHCN, establishing alow-dimensional range as a valid solutions manifold. This manifold maintains physiological excitability through compensatorychanges in ion channel expression, corresponding to the experimental observations. Our study highlights how conductanceimbalances can induce dysfunctional dynamics in basal ganglia circuits. This analysis provides an important starting pointfor future research into neurodegenerative diseases where alterations in intrinsic conductance regulation are likely to have asignificant impact. Biological sciences/Biological techniques Biological sciences/Computational biology and bioinformatics Physical sciences/Engineering Biological sciences/Neuroscience Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementaryinformation.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 19 Dec, 2025 Reviewers agreed at journal 01 Dec, 2025 Reviews received at journal 26 Nov, 2025 Reviewers agreed at journal 24 Nov, 2025 Reviews received at journal 01 Oct, 2025 Reviewers agreed at journal 01 Oct, 2025 Reviewers agreed at journal 01 Oct, 2025 Reviewers invited by journal 28 Sep, 2025 Editor invited by journal 03 Sep, 2025 Editor assigned by journal 30 Aug, 2025 Submission checks completed at journal 29 Aug, 2025 First submitted to journal 27 Aug, 2025 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-7471232","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":526804761,"identity":"6d88e25e-ec16-43b3-8889-41303cf2d361","order_by":0,"name":"Matheus Sousa","email":"","orcid":"","institution":"Federal University of Rio Grande do Norte","correspondingAuthor":false,"prefix":"","firstName":"Matheus","middleName":"","lastName":"Sousa","suffix":""},{"id":526804762,"identity":"812c3617-1f41-4ba3-8481-2748ea8b09b0","order_by":1,"name":"Gabriel Cunha","email":"","orcid":"","institution":"Federal University of Rio Grande do 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Leak–HCN Conductance Correlations","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific 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Acknowledging these diversesubpopulations has altered comprehension of the GPe, demonstrating its variability and importance in typical and atypical states.In this study, we analyzed, using the Hodgkin-Huxley like model, the dynamics of these two GPe neuron subtypes, scanningconductance values for two ion channels: the leak (gleak) and the HCN (gHCN). We identified, through parameter space gleak vs.gHCN, values of intrinsic electrophysiological responses for each neuronal subtype, such as firing rate, sag-ratio, and troughpotential. With this, we developed a method for intersecting parameter spaces, which finds a subset of electrophysiologicalresults.Finally, from this subset of results, we extracted the linear inverse correlation between gleak and gHCN, establishing alow-dimensional range as a valid solutions manifold. This manifold maintains physiological excitability through compensatorychanges in ion channel expression, corresponding to the experimental observations. Our study highlights how conductanceimbalances can induce dysfunctional dynamics in basal ganglia circuits. 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