Abstract

ABSTRACTThe prevalence and importance of hearing damage caused by noise levels not previously thought to cause permanent hearing impairment has become apparent in recent years. The damage to, and loss of, afferent terminals of auditory nerve fibres at the cochlear inner hair cell has been well established, but the effects of noise exposure and terminal loss on the inner hair cell are less known. Using three-dimensional structural studies in mice we have examined the consequences of afferent terminal damage on inner hair cell morphology and intracellular structure. We identified a structural phenotype in the pre-synaptic regions of these damaged hair cells that persists for four weeks after noise exposure, and demonstrates a specific dysregulation of the synaptic vesicle recycling pathway. We show evidence of a failure in regeneration of vesicles from small membrane cisterns in damaged terminals, resulting from a failure of separation of small vesicle buds from the larger cisternal membranes.

Highlights

  • Inner hair cells (IHC) are the principal receptor cells in the mammalian cochlea

  • Noise exposed cells show significant changes to cell shape, but not organelle distribution Auditory threshold, the lowest sound pressure level that evokes a neural response, can be estimated from recordings of the auditory brainstem response (ABR) that reflects the neural activity evoked by an auditory stimulus

  • Midmodiolar sections through the noise damaged region were cut for serial block face-scanning electron microscopy (SBF-SEM) and for electron tomography

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Summary

Introduction

Inner hair cells (IHC) are the principal receptor cells in the mammalian cochlea. They detect fluid motion induced by sound vibrations and transduce it into neural impulses that are relayed to the brain. The presynaptic (IHC) side of the synapse is characterised by a synaptic ribbon, a rounded or linear structure to which neurotransmitter vesicles are tethered and thereby held close to the presynaptic membrane (Matsubara et al, 1996). This is thought to enable the rapid and prolonged (indefatigable) release of neurotransmitter onto the clusters of AMPA-type glutamate receptors on the opposing post-synaptic membrane with the consequent continuous and persistent neural stimulation necessary for perception of auditory information

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