Targeted Neuronal Stimulation Modulates Working Memory via Astrocytic Interactions: Insights from a Spiking Neuron-Astrocyte Model

Targeted Neuronal Stimulation Modulates Working Memory via Astrocytic Interactions: Insights from a Spiking Neuron-Astrocyte Model | 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 Targeted Neuronal Stimulation Modulates Working Memory via Astrocytic Interactions: Insights from a Spiking Neuron-Astrocyte Model Mahmood Amiri, Pedram Naghieh, Herbert Peremans This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7065469/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 Brain stimulation is a promising approach to cognitive enhancement, particularly for improving working memory (WM) function. However, conventional stimulation paradigms often overlook the active contributions of astrocytes and treat stimulation as an all-or-none intervention without considering spatial information or studying the competition among temporal dynamics. In this study, we employ a spiking neuron-astrocyte network model comprising excitatory neurons, inhibitory neurons, astrocytes, and integrated recording and stimulation electrodes within a 2D structure. This framework allows us to investigate how targeted neuronal stimulation modulates WM via neuroglial interactions. We demonstrate that WM emerges from a hierarchy of temporal dynamics: rapid neuronal spiking, intermediate synaptic glutamate release, and slow astrocytic calcium signaling. Through targeted neuronal stimulation across three experiments, we demonstrate that: (1) Excitatory stimulation enhances WM in synaptically impaired networks by restoring both astrocytic calcium dynamics and neuronal activity through boosting the functionality of abnormal synapses. (2) Inhibitory stimulation in healthy networks suppresses excitatory neuronal firing, blocks the neuroglial feedback loop necessary for WM maintenance, and shows how transient inhibition morphs into lasting dysfunction. Interestingly, we found that delayed reaction of dynamics can serve as a defense mechanism against such disruptions, highlighting the protective role of the temporal buffer in neuroglial networks. (3) Excitatory stimulation during training augments the encoding process by elevating astrocytic calcium levels associated with novel input patterns, thereby improving WM performance. To our knowledge, this study is the first to examine WM manipulation through neuronal stimulation while posing astrocytes as key mediators. Our findings underscore the necessity for spatiotemporal precision in neuronal stimulation protocols that leverage competing neuroglial temporal dynamics for cognitive enhancement, therapeutic interventions, and bioinspired systems. Biological sciences/Neuroscience/Computational neuroscience Physical sciences/Engineering/Biomedical engineering Astrocytes working memory spiking neural network neural stimulation Full Text Additional Declarations There is NO Competing Interest. Supplementary Files NaghiehStimWMsupplimentaryV4.docx SUPPLEMENTARY INFORMATION StimWMV63E1CondensedExplanationsWorkingMemoryInputPattern.mp4 SUPPLEMENTARY VIDEO 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-7065469","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":481907000,"identity":"fc0b91c5-52c1-485f-b655-88ff4b38c65b","order_by":0,"name":"Mahmood Amiri","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYBACgwNgkoGHQQJIf2BgSCCoxRJZC+MMYrTYH4CxgFqYeYjRYnb8AOOnGwX3ZBikuxMf27bZ5fGzNzB++JiDR8uZBGbpHINiHgaZs5uNc9uSiyV7DjBLztyGR8uBBAaglgSgX3K3See2MSduuJHAxsyLR4vB+QfMv6Fatv+2bKsnQgtQAdwWZsa2w8RoecBmDdYC9Itkz7njiTN7Djbj9YvB+QTm2zl/EuwZpHs3fvhRVp3Yz9588MNHPFoYGPg/gClwBDGygZiMDfjUo4M/pCgeBaNgFIyCkQIAlOtRDfI/EokAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-1720-0060","institution":"University of Antwerp","correspondingAuthor":true,"prefix":"","firstName":"Mahmood","middleName":"","lastName":"Amiri","suffix":""},{"id":481907001,"identity":"e8ff3085-0dac-440d-8806-851a29776737","order_by":1,"name":"Pedram Naghieh","email":"","orcid":"","institution":"University of Antwerp","correspondingAuthor":false,"prefix":"","firstName":"Pedram","middleName":"","lastName":"Naghieh","suffix":""},{"id":481907002,"identity":"8e7d882c-492b-4877-a9e6-dd6009475f10","order_by":2,"name":"Herbert Peremans","email":"","orcid":"","institution":"University of Antwerp","correspondingAuthor":false,"prefix":"","firstName":"Herbert","middleName":"","lastName":"Peremans","suffix":""}],"badges":[],"createdAt":"2025-07-07 12:36:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7065469/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7065469/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88048724,"identity":"c13e0ada-666c-49db-96e7-77f418026a48","added_by":"auto","created_at":"2025-07-31 19:08:27","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1967923,"visible":true,"origin":"","legend":"","description":"","filename":"NaghiehStimWMmainV12NMI.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7065469/v1_covered_ccbca9a6-be5b-4794-9483-391f0f1a45b7.pdf"},{"id":86246747,"identity":"996ec29a-5236-4097-9517-ebdbb4512328","added_by":"auto","created_at":"2025-07-08 11:49:04","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2388858,"visible":true,"origin":"","legend":"SUPPLEMENTARY INFORMATION","description":"","filename":"NaghiehStimWMsupplimentaryV4.docx","url":"https://assets-eu.researchsquare.com/files/rs-7065469/v1/e74afc9f54eb877268c46c8f.docx"},{"id":86246748,"identity":"01aa6b4a-ec20-4f2e-8187-294525c8c929","added_by":"auto","created_at":"2025-07-08 11:49:04","extension":"mp4","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":17552253,"visible":true,"origin":"","legend":"SUPPLEMENTARY VIDEO","description":"","filename":"StimWMV63E1CondensedExplanationsWorkingMemoryInputPattern.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7065469/v1/42de204d316b48fd23137e1a.mp4"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Targeted Neuronal Stimulation Modulates Working Memory via Astrocytic Interactions: Insights from a Spiking Neuron-Astrocyte Model","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Astrocytes, working memory, spiking neural network, neural stimulation","lastPublishedDoi":"10.21203/rs.3.rs-7065469/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7065469/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Brain stimulation is a promising approach to cognitive enhancement, particularly for improving working memory (WM) function. 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