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This study examines the first synapses of the central auditory pathway, endbulbs of Held formed by auditory nerve afferents onto bushy cells in the cochlear nucleus. Using electrophysiology and immunolabelling, the work shows altered endbulb function, including reduced vesicle release probability and an enlarged releasable vesicle pool. Serial blockface electron microscopy reveals increased presynaptic synaptic vesicle density near terminals after noise, without detectable changes in contact area or active zone and postsynaptic density numbers, supporting a homeostatic structural basis for sustained synaptic efficacy during high activity.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ultrastructural-changes-at-auditory-nerve-synapses-following-moderate-noise-exposure/444845/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/ultrastructural-changes-at-auditory-nerve-synapses-following-moderate-noise-exposure/444845.png","ImageObject",300,407,{"name":92,"@type":93},"Rainbow Cat","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What synapses are analyzed after moderate noise exposure?","Question",{"text":113,"@type":114},"The study focuses on endbulbs of Held, the first central auditory synapses where auditory nerve afferents contact bushy cells in the cochlear nucleus.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What physiological changes are observed at endbulbs of Held?",{"text":118,"@type":114},"Moderate noise exposure decreases the probability of vesicle release while increasing the pool of releasable vesicles, based on electrophysiological and immunolabelling measures.",{"name":120,"@type":111,"acceptedAnswer":121},"How do the structural findings relate to the larger vesicle pool?",{"text":122,"@type":114},"Serial blockface electron microscopy shows no changes in synaptic contact area or in the number/density of active zones and postsynaptic densities, but terminals become darker with noise, indicating higher synaptic vesicle density near release sites.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},444845,1790921075,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":31,"preview_page_count":4},962090769181,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.30.697061](https://doi.org/10.64898/2025.12.30.697061); this version posted December 31, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY 4.0 International license.  \nUltrastructural changes at auditory nerve synapses following moderate noise exposure  \nDenesha Gorman5, Nicole F. Wong 1, Colin W. Schupbach 1, Stacy L. DiCenso 1, Sophie C. XuFriedman 1, Kevin M. Boergens5,6, Amanda M. Lauer2,3,4, Angeles Salles5*, Matthew A. XuFriedman 1*  \n1Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260  \n2Department of Otolaryngology-HNS, Johns Hopkins University School of Medicine, Baltimore, MD 21205  \n3The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205  \n4Center for Functional Anatomy and Evolution, Johns Hopkins University School of Medicine, Baltimore, MD 21205  \n5Department of Biological Sciences, University of Illinois Chicago, Chicago, IL, 60607 6Department of Physics, University of Illinois Chicago, Chicago, IL, 60607  \n*Co-Corresponding authors  \nE-mails: [salles@uic.edu](salles@uic.edu), [mx@buffalo.edu](mx@buffalo.edu)  \n[Number of pages: 19](Number of pages: 19)  \n[Number of figures: 4](Number of figures: 4)  \n[Number of tables: 0](Number of tables: 0)  \nbioRxiv preprint doi: [https://doi.org/10.64898/2025.12.30.697061](https://doi.org/10.64898/2025.12.30.697061); this version posted December 31, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY 4.0 International license.  \nNumber of words  \nAbstract: 194, significance statement: 160, introduction: 350, discussion: 913  \nKeywords: cochlear nucleus, endbulb of Held, bushy cell, postsynaptic density, serial blockface electron microscopy  \nAuthor contributions  \nDG, NFW, CWS, SLD, SCX annotated electron microscopy material; AS, AML, KMB, and MAX-F planned the research; DG, AS, AML, KMB, and MAX-F wrote the paper.  \nAcknowledgements  \nThe authors thank Connor Cook for assistance with histology, Austin D’Angelo, Treefa Shwani, Jarrod Lynch, Daysia Augustin, and Aaron Lee for advice about annotation. This work was supported by National Institutes of Health grants R01 DC015508 (MXF) and the George T.  \nNager endowment (AML) .  \nAbstract  \nModerate noise exposure is a common experience, yet its impact on central auditory synapses remains poorly understood. We study this issue at the first synapses in the central auditory pathway formed by auditory nerve afferents onto bushy cells in the cochlear nucleus, called endbulbs of Held. Non-traumatic noise exposure alters endbulb properties, decreasing the probability of vesicle release and enlarging the pool of releasable vesicles as assessed using electrophysiological methods and immunolabelling. These changes appear homeostatic, to  \nbioRxiv preprint doi: [https://doi.org/10.64898/2025.12.30.697061](https://doi.org/10.64898/2025.12.30.697061); this version posted December 31, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY 4.0 International license.  \nmaintain synaptic efficacy during periods of high activity. To identify structural changes underlying the larger vesicle pool, we used serial blockface electron microscopy of endbulbs from control and noise-exposed mice to quantitatively assess synaptic morphology. We observed no differences in the juxtapositional area between endbulbs and bushy cells, nor in the number or density of active zones and postsynaptic densities. Imag","cbCair1k3Q1UglGx","https://ap.wps.com/l/cbCair1k3Q1UglGx","pdf",1087138,"English","# Abstract\n# Significance statement\n# Introduction\n# Discussion","[{\"question\":\"What synapses are analyzed after moderate noise exposure?\",\"answer\":\"The study focuses on endbulbs of Held, the first central auditory synapses where auditory nerve afferents contact bushy cells in the cochlear nucleus.\"},{\"question\":\"What physiological changes are observed at endbulbs of Held?\",\"answer\":\"Moderate noise exposure decreases the probability of vesicle release while increasing the pool of releasable vesicles, based on electrophysiological and immunolabelling measures.\"},{\"question\":\"How do the structural findings relate to the larger vesicle pool?\",\"answer\":\"Serial blockface electron microscopy shows no changes in synaptic contact area or in the number/density of active zones and postsynaptic densities, but terminals become darker with noise, indicating higher synaptic vesicle density near release sites.\"}]","Ultrastructural changes at auditory nerve synapses following moderate noise exposure | PDF",1790709458]