title: Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus.
abstract: 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.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA; Department of Otorhinolaryngology-Head and Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Kurioka
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Amarins N
authors.initials: AN
authors.lastname: Heeringa
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Beyer
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Swiderski
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Ariane C
authors.initials: AC
authors.lastname: Kanicki
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Kabara
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Dolan
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Shore
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA. Electronic address: yoash@umich.edu.
authors.forename: Yehoash
authors.initials: Y
authors.lastname: Raphael
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000378:metabolism / Q000473:pathology*; D048429:Cell Size; D002470:Cell Survival; D003051:Cochlea / Q000378:metabolism / Q000473:pathology*; D017626:Cochlear Nucleus / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000473:pathology*; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009622:Noise / Q000009:adverse effects*; D018091:Receptors, AMPA / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; C104722:glutamate receptor ionotropic, AMPA 2
keywords: auditory nerve fiber; cochlear nucleus; myelin; noise exposure; selective hair cell ablation; synapse