A novel and evolutionarily conserved inhibitory circuit selectively regulates dentate gyrus mossy cell function

A novel and evolutionarily conserved inhibitory circuit selectively regulates dentate gyrus mossy cell function | 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 A novel and evolutionarily conserved inhibitory circuit selectively regulates dentate gyrus mossy cell function Geoffrey Vargish, Haley Rice, Xiaoqing Yuan, Steven Hunt, Adam Caccavano, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7268106/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 The mammalian dentate gyrus contributes to mnemonic function by parsing similar events and places. The disparate activity patterns of mossy cells and granule cells are believed to enable this function yet the mechanisms that drive this circuit dynamic remain elusive. We identified a novel inhibitory interneuron subtype, characterized by VGluT3 expression, with overwhelming target selectivity for mossy cells while also revealing that CCK, PV, SST and VIP interneurons preferentially innervate granule cells. Leveraging pharmacology and novel enhancer viruses, we find that this target-specific inhibitory innervation pattern is evolutionarily conserved in non-human primates and humans. In addition, in vivo chemogenetic manipulation of VGluT3+ interneurons selectively alters the activity and functional properties of mossy cells. These findings establish that mossy cells and granule cells have unique, evolutionarily conserved inhibitory innervation patterns and suggest selective inhibitory circuits may be necessary to maintain DG circuit dynamics and enable pattern separation across species. Biological sciences/Neuroscience/Neural circuits Biological sciences/Neuroscience/Cellular neuroscience Biological sciences/Neuroscience/Learning and memory/Hippocampus Full Text Additional Declarations There is NO Competing Interest. 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. We do this by developing innovative software and high quality services for the global research community. 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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-7268106","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":497793339,"identity":"caeccf54-0b63-4aec-be7c-3e4d9c6bafa0","order_by":0,"name":"Geoffrey 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