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Ouabain-Induced Cochlear Nerve Degeneration: Synaptic Loss and Plasticity in a Mouse Model of Auditory Neuropathy

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Abstract

Ouabain application to the round window can selectively destroy type-I spiral ganglion cells, producing an animal model of auditory neuropathy. To assess the long-term effects of this deafferentation on synaptic organization in the organ of Corti and cochlear nucleus, and to ask whether surviving cochlear neurons show any post-injury plasticity in the adult, we quantified the peripheral and central synapses of type-I neurons at posttreatment times ranging from 1 to 3 months. Measures of normal DPOAEs and greatly reduced auditory brainstem responses (ABRs) confirmed the neuropathy phenotype. Counts of presynaptic ribbons and postsynaptic glutamate receptor patches in the inner hair cell area decreased with post-exposure time, as did counts of cochlear nerve terminals in the cochlear nucleus. Although these counts provided no evidence of new synapse formation via branching from surviving neurons, the regular appearance of ectopic neurons in the inner hair cell area suggested that neurite extension is not uncommon. Correlations between pathophysiology and histopathology showed that ABR thresholds are very insensitive to even massive neural degeneration, whereas the amplitude of ABR wave 1 is a better metric of synaptic degeneration.

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Acknowledgments

This work was supported by grants from the National Institute on Deafness and other Communicative Disorders: RO1 DC007174 (AE), R01 DC 00188 (MCL), R01 DC009836 (DBP), and P30 DC05209 (MCL).

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Authors and Affiliations

  1. Department of Otology and Laryngology, Harvard Medical School, Boston, MA, 02115, USA

    Yasheng Yuan, Fuxin Shi, Yanbo Yin, Mingjie Tong, Daniel B. Polley, M. Charles Liberman & Albert S.B. Edge

  2. Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA, 02114, USA

    Yasheng Yuan, Fuxin Shi, Yanbo Yin, Mingjie Tong, Daniel B. Polley, M. Charles Liberman & Albert S.B. Edge

  3. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA

    Hainan Lang

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  1. Yasheng Yuan
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  2. Fuxin Shi
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  3. Yanbo Yin
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  4. Mingjie Tong
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Correspondence to Albert S.B. Edge.

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M. Charles Liberman and Albert S.B. Edge contributed equally to this work.

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Yuan, Y., Shi, F., Yin, Y. et al. Ouabain-Induced Cochlear Nerve Degeneration: Synaptic Loss and Plasticity in a Mouse Model of Auditory Neuropathy. JARO 15, 31–43 (2014). https://doi.org/10.1007/s10162-013-0419-7

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  • DOI: https://doi.org/10.1007/s10162-013-0419-7

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