Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus.
In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non-sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochlear nucleus (CN). However, it is not clear whether loss of HCs alone leads to secondary degeneration in these neural components of the auditory pathway. To elucidate this issue, we investigated changes of central components after cochlear insults specific to HCs using diphtheria toxin receptor (DTR) mice expressing DTR only in HCs and exhibiting complete HC loss when injected with diphtheria toxin (DT). We showed that DT-induced HC ablation has no significant impacts on the survival of auditory neurons, central synaptic terminals, and myelin, despite complete HC loss and profound deafness. In contrast, noise exposure induced significant changes in synapses, myelin and CN organization even without loss of inner HCs. We observed a decrease of neuronal size in the auditory pathway, including peripheral axons, spiral ganglion neurons, and CN neurons, likely due to loss of input from the cochlea. Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination.
['Kurioka|Takaomi|T|', 'Lee|Min Young|MY|', 'Heeringa|Amarins N|AN|', 'Beyer|Lisa A|LA|', 'Swiderski|Donald L|DL|', 'Kanicki|Ariane C|AC|', 'Kabara|Lisa L|LL|', 'Dolan|David F|DF|', 'Shore|Susan E|SE|', 'Raphael|Yehoash|Y|']
D000818:Animals D001306:Auditory Pathways D048429:Cell Size D002470:Cell Survival D003051:Cochlea D017626:Cochlear Nucleus D004195:Disease Models, Animal D016057:Evoked Potentials, Auditory, Brain Stem D005260:Female D006198:Hair Cells, Auditory D006317:Hearing Loss, Noise-Induced D007150:Immunohistochemistry D008297:Male D008822:Mice, Transgenic D046529:Microscopy, Electron, Transmission D009622:Noise D018091:Receptors, AMPA D050598:Vesicular Glutamate Transport Protein 1
selective hair cell ablation noise exposure cochlear nucleus auditory nerve fiber myelin synapse