title: The reduced cochlear output and the failure to adapt the central auditory response causes tinnitus in noise exposed rats.
abstract: Tinnitus is proposed to be caused by decreased central input from the cochlea, followed by increased spontaneous and evoked subcortical activity that is interpreted as compensation for increased responsiveness of central auditory circuits. We compared equally noise exposed rats separated into groups with and without tinnitus for differences in brain responsiveness relative to the degree of deafferentation in the periphery. We analyzed (1) the number of CtBP2/RIBEYE-positive particles in ribbon synapses of the inner hair cell (IHC) as a measure for deafferentation; (2) the fine structure of the amplitudes of auditory brainstem responses (ABR) reflecting differences in sound responses following decreased auditory nerve activity and (3) the expression of the activity-regulated gene Arc in the auditory cortex (AC) to identify long-lasting central activity following sensory deprivation. Following moderate trauma, 30% of animals exhibited tinnitus, similar to the tinnitus prevalence among hearing impaired humans. Although both tinnitus and no-tinnitus animals exhibited a reduced ABR wave I amplitude (generated by primary auditory nerve fibers), IHCs ribbon loss and high-frequency hearing impairment was more severe in tinnitus animals, associated with significantly reduced amplitudes of the more centrally generated wave IV and V and less intense staining of Arc mRNA and protein in the AC. The observed severe IHCs ribbon loss, the minimal restoration of ABR wave size, and reduced cortical Arc expression suggest that tinnitus is linked to a failure to adapt central circuits to reduced cochlear input.
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen (THRC), Molecular Physiology of Hearing, University of Tübingen, Tübingen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Rüttiger
authors.forename: Wibke
authors.initials: W
authors.lastname: Singer
authors.forename: Rama
authors.initials: R
authors.lastname: Panford-Walsh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Sze Chim
authors.initials: SC
authors.lastname: Lee
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zuccotti
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zimmermann
authors.forename: Mirko
authors.initials: M
authors.lastname: Jaumann
authors.forename: Karin
authors.initials: K
authors.lastname: Rohbock
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism; D001309:Auditory Threshold; D001522:Behavior, Animal; D003051:Cochlea / Q000378:metabolism / Q000503:physiopathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism; D006317:Hearing Loss, Noise-Induced / Q000503:physiopathology; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009622:Noise / Q000009:adverse effects*; D051381:Rats; D014012:Tinnitus / Q000209:etiology* / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein