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Histological Correlates of Auditory Nerve Injury from Kainic Acid in the Budgerigar (Melopsittacus undulatus)

Journal of the Association for Research in Otolaryngology (2023)Cite this article

Abstract

Purpose

Loss of auditory nerve afferent synapses with cochlear hair cells, called cochlear synaptopathy, is a common pathology in humans caused by aging and noise overexposure. The perceptual consequences of synaptopathy in isolation from other cochlear pathologies are still unclear. Animal models provide an effective approach to resolve uncertainty regarding the physiological and perceptual consequences of auditory nerve loss, because neural lesions can be induced and readily quantified. The budgerigar, a parakeet species, has recently emerged as an animal model for synaptopathy studies based on its capacity for vocal learning and ability to behaviorally discriminate simple and complex sounds with acuity similar to humans. Kainic acid infusions in the budgerigar produce a profound reduction of compound auditory nerve responses, including wave I of the auditory brainstem response, without impacting physiological hair cell measures. These results suggest selective auditory nerve damage. However, histological correlates of neural injury from kainic acid are still lacking.

Methods

We quantified the histological effects caused by intracochlear infusion of kainic acid (1 mM; 2.5 µL), and evaluated correlations between the histological and physiological assessments of auditory nerve status.

Results

Kainic acid infusion in budgerigars produced pronounced loss of neural auditory nerve soma (60% on average) in the cochlear ganglion, and of peripheral axons, at time points 2 or more months following injury. The hair cell epithelium was unaffected by kainic acid. Neural loss was significantly correlated with reduction of compound auditory nerve responses and auditory brainstem response wave I.

Conclusion

Compound auditory nerve responses and wave I provide a useful index of cochlear synaptopathy in this animal model.

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Data Availability

Data in the manuscript are available by request from the corresponding author.

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Acknowledgements

Robert Dirksen provided use of his cryostat for frozen sectioning of cochlear samples.

Funding

This research was supported by grant R01-DC017519.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA

    Yingxuan Wang & Kenneth S. Henry

  2. Department of Neuroscience, University of Rochester, Rochester, NY 14642, USA

    Kristina S. Abrams & Kenneth S. Henry

  3. Department of Otolaryngology, University of Rochester, Rochester, NY 14642, USA

    Margaret Youngman & Kenneth S. Henry

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  1. Yingxuan Wang
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  4. Kenneth S. Henry
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Correspondence to Kenneth S. Henry.

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Wang, Y., Abrams, K.S., Youngman, M. et al. Histological Correlates of Auditory Nerve Injury from Kainic Acid in the Budgerigar (Melopsittacus undulatus). JARO (2023). https://doi.org/10.1007/s10162-023-00910-5

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