title: Noise-induced inner hair cell ribbon loss disturbs central arc mobilization: a novel molecular paradigm for understanding tinnitus.
abstract: Increasing evidence shows that hearing loss is a risk factor for tinnitus and hyperacusis. Although both often coincide, a causal relationship between tinnitus and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are assumed to be caused by elevated responsiveness in subcortical circuits. We examined both the impact of different degrees of cochlear damage and the influence of stress priming on tinnitus induction. We used (1) a behavioral animal model for tinnitus designed to minimize stress, (2) ribbon synapses in inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of auditory brainstem responses (ABR) to detect differences in stimulus-evoked neuronal activity, (4) the expression of the activity-regulated cytoskeletal protein, Arc, to identify long-lasting changes in network activity within the basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5) stress priming to investigate the influence of corticosteroid on trauma-induced brain responses. We observed that IHC ribbon loss (deafferentation) leads to tinnitus when ABR functions remain reduced and Arc is not mobilized in the hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc is mobilized, tinnitus does not occur. Both central response patterns were found to be independent of a profound threshold loss and could be shifted by the corticosterone level at the time of trauma. We, therefore, discuss the findings in the context of a history of stress that can trigger either an adaptive or nonadaptive brain response following injury.
authors.affiliation: Molecular Physiology of Hearing, Hearing Research Centre Tübingen (THRC), Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany.
authors.forename: Wibke
authors.initials: W
authors.lastname: Singer
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zuccotti
authors.forename: Mirko
authors.initials: M
authors.lastname: Jaumann
authors.forename: Sze Chim
authors.initials: SC
authors.lastname: Lee
authors.forename: Rama
authors.initials: R
authors.lastname: Panford-Walsh
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zimmermann
authors.forename: Christoph
authors.initials: C
authors.lastname: Franz
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Geisler
authors.forename: Iris
authors.initials: I
authors.lastname: Köpschall
authors.forename: Karin
authors.initials: K
authors.lastname: Rohbock
authors.forename: Ksenya
authors.initials: K
authors.lastname: Varakina
authors.forename: Sandrine
authors.initials: S
authors.lastname: Verpoorten
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinbothe
authors.forename: Thomas
authors.initials: T
authors.lastname: Schimmang
authors.forename: Lukas
authors.initials: L
authors.lastname: Rüttiger
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001309:Auditory Threshold; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism / Q000473:pathology*; D034381:Hearing Loss / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009622:Noise / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D014012:Tinnitus / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein