Ultrastructural changes at auditory nerve synapses following moderate noise exposure

Sep 29, 2026

Moderate noise exposure is common, but its effects on central auditory synapses remain insufficiently defined. 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.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Significance statement

Introduction

Discussion

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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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 available under aCC-BY 4.0 International license. Ultrastructural changes at auditory nerve synapses following moderate noise exposure Denesha 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* 1Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 2Department of Otolaryngology-HNS, Johns Hopkins University School of Medicine, Baltimore, MD 21205 3The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205 4Center for Functional Anatomy and Evolution, Johns Hopkins University School of Medicine, Baltimore, MD 21205 5Department of Biological Sciences, University of Illinois Chicago, Chicago, IL, 60607 6Department of Physics, University of Illinois Chicago, Chicago, IL, 60607 *Co-Corresponding authors E-mails: [salles@uic.edu](salles@uic.edu), [mx@buffalo.edu](mx@buffalo.edu) [Number of pages: 19](Number of pages: 19) [Number of figures: 4](Number of figures: 4) [Number of tables: 0](Number of tables: 0) 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 available under aCC-BY 4.0 International license. Number of words Abstract: 194, significance statement: 160, introduction: 350, discussion: 913 Keywords: cochlear nucleus, endbulb of Held, bushy cell, postsynaptic density, serial blockface electron microscopy Author contributions DG, 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. Acknowledgements The 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. Nager endowment (AML) . Abstract Moderate 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 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 available under aCC-BY 4.0 International license. maintain 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

FAQs

What synapses are analyzed after moderate noise exposure?

The study focuses on endbulbs of Held, the first central auditory synapses where auditory nerve afferents contact bushy cells in the cochlear nucleus.

What physiological changes are observed at endbulbs of Held?

Moderate noise exposure decreases the probability of vesicle release while increasing the pool of releasable vesicles, based on electrophysiological and immunolabelling measures.

How do the structural findings relate to the larger vesicle pool?

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.

Sep 29, 2026

Uploaded by Rainbow Cat