Noise-induced ribbon synapse loss in the mouse basal cochlear region does not reduce inner hair cell exocytosis

David Oestreicher; Alfonso Mauro Malpede; Annalena Reitmeier; Carolin Paula Bräuer; Laura Schoch; Nicola Strenzke; Tina Pangrsic

doi:10.3389/fncel.2024.1523978

Noise-induced ribbon synapse loss in the mouse basal cochlear region does not reduce inner hair cell exocytosis

Front Cell Neurosci. 2025 Jan 7:18:1523978. doi: 10.3389/fncel.2024.1523978. eCollection 2024.

Authors

David Oestreicher^{1

2}, Alfonso Mauro Malpede^{1

2}, Annalena Reitmeier^{1

2}, Carolin Paula Bräuer^{1

2}, Laura Schoch^{1

2}, Nicola Strenzke^{3

4}, Tina Pangrsic^{1

2

4}

Affiliations

¹ Experimental Otology Group, InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, Göttingen, Germany.
² Auditory Neuroscience Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
³ Auditory Systems Physiology Group, Institute for Auditory Neuroscience, InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
⁴ Collaborative Research Center 889, University of Göttingen, Göttingen, Germany.

Abstract

Noise-induced hearing loss is one of the most common forms of hearing loss in adults and also one of the most common occupational diseases. Extensive previous work has shown that the highly sensitive synapses of the inner hair cells (IHCs) may be the first target for irreparable damage and permanent loss in the noise-exposed cochlea, more precisely in the cochlear base. However, how such synaptic loss affects the synaptic physiology of the IHCs in this particularly vulnerable part of the cochlea has not yet been investigated. To address this question, we exposed 3-4-week-old C57BL/6J mice to 8-16 kHz noise for 2 h under isoflurane anesthesia. We then employed hearing measurements, immunohistochemistry and patch-clamp to assess IHC synaptic function. Two noise sound pressure levels (SPLs) were used to evoke acute hearing threshold elevations with different levels of recovery 2 weeks post-exposure. Regardless of noise intensity, the exposure resulted in a loss of approximately 25-36% of ribbon synapses in the basal portions of the cochlea that persisted 2 weeks after exposure. Perforated patch-clamp recordings were made in the IHCs of the basal regions of the cochlea where the greatest synaptic losses were observed. Depolarization-evoked calcium currents in IHCs 2 weeks after exposure were slightly but not significantly smaller as compared to controls from age-matched non-exposed animals. Exocytic changes monitored as changes in membrane capacitance did not follow that trend and remained similar to controls despite significant loss of ribbons, likely reflecting increased exocytosis at the remaining synapses. Additionally, we report for the first time that acute application of isoflurane reduces IHC calcium currents, which may have implications for noise-induced IHC synaptic loss.

Keywords: calcium channel; inner hair cell; isoflurane; noise trauma; ribbon synapse.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants of the German Research Foundation through the collaborative research center 889 (B09 to TP), and the Clinician Scientist Program “Cell Dynamics in Disease and Therapy” at the University Medical Center Göttingen (project number 413501650 to DO).