Is cochlear synapse loss an origin of low-frequency hearing loss associated with endolymphatic hydrops?

Carla V. Valenzuela, Choongheon Lee, Abby Mispagel, Atri Bhattacharyya, Shannon M. Lefler, Shelby Payne, Shawn S. Goodman, Amanda J. Ortmann, Craig A. Buchman, Mark A. Rutherford, Jeffery T. Lichtenhan

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


There is a strong association between endolymphatic hydrops and low-frequency hearing loss, but the origin of the hearing loss remains unknown. A reduction in the number of cochlear afferent synapses between inner hair cells and auditory nerve fibres may be the origin of the low-frequency hearing loss, but this hypothesis has not been directly tested in humans or animals. In humans, measurements of hearing loss and postmortem temporal-bone based measurements of endolymphatic hydrops are generally separated by large amounts of time. In animals, there has not been a good objective, physiologic, and minimally invasive measurement of low-frequency hearing. We overcame this obstacle with the combined use of a reliable surgical approach to ablate the endolymphatic sac in guinea pigs and create endolymphatic hydrops, the Auditory Nerve Overlapped Waveform to measure low-frequency hearing loss (≤ 1 kHz), and immunohistofluorescence-based confocal microscopy to count cochlear synapses. Results showed low- and mid-(1–4 kHz) frequency hearing loss at all postoperative days, 1, 4, and 30. There was no statistically significant loss of cochlear synapses, and there was no correlation between synapse loss and hearing function. We conclude that cochlear afferent synaptic loss is not the origin of the low-frequency hearing loss in the early days following endolymphatic sac ablation. Understanding what is, and is not, the origin of a hearing loss can help guide preventative and therapeutic development.

Original languageEnglish
Article number108099
JournalHearing research
StatePublished - Dec 2020


  • Auditory Nerve Overlapped Waveform
  • Endolymphatic hydrops
  • Low-frequency hearing loss
  • Ménière's disease
  • Ribbon synapse


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