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Ouabain-induced cochlear nerve degeneration: synaptic loss and plasticity in a mouse model of auditory neuropathy.

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.

Pubmed ID: 24113829 RIS Download

Mesh terms: Animals | Cochlea | Cochlear Nerve | Disease Models, Animal | Enzyme Inhibitors | Female | Mice | Mice, Inbred CBA | Nerve Degeneration | Neuronal Plasticity | Organ of Corti | Ouabain | Presynaptic Terminals | Receptors, Glutamate | Synapses | Time Factors | Vestibulocochlear Nerve Injuries

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Associated grants

  • Agency: NIDCD NIH HHS, Id: R01 DC007174
  • Agency: NIDCD NIH HHS, Id: P50 DC000422
  • Agency: NIDCD NIH HHS, Id: R01 DC 00188
  • Agency: NIDCD NIH HHS, Id: R01 DC000188
  • Agency: NIDCD NIH HHS, Id: P30 DC05209
  • Agency: NIDCD NIH HHS, Id: R01 DC012058
  • Agency: NIDCD NIH HHS, Id: R01 DC009836
  • Agency: NIDCD NIH HHS, Id: P30 DC005209

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