Molecular Neurobiology

, Volume 47, Issue 1, pp 261–279 | Cite as

Noise-Induced Inner Hair Cell Ribbon Loss Disturbs Central Arc Mobilization: A Novel Molecular Paradigm for Understanding Tinnitus

  • Wibke Singer
  • Annalisa Zuccotti
  • Mirko Jaumann
  • Sze Chim Lee
  • Rama Panford-Walsh
  • Hao Xiong
  • Ulrike Zimmermann
  • Christoph Franz
  • Hyun-Soon Geisler
  • Iris Köpschall
  • Karin Rohbock
  • Ksenya Varakina
  • Sandrine Verpoorten
  • Thomas Reinbothe
  • Thomas Schimmang
  • Lukas Rüttiger
  • Marlies Knipper


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.


Tinnitus Hyperacusis Stress Arc Ribbon synapse Behavioral animal model 

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Wibke Singer
    • 1
  • Annalisa Zuccotti
    • 1
  • Mirko Jaumann
    • 1
  • Sze Chim Lee
    • 1
  • Rama Panford-Walsh
    • 1
  • Hao Xiong
    • 1
  • Ulrike Zimmermann
    • 1
  • Christoph Franz
    • 1
  • Hyun-Soon Geisler
    • 1
  • Iris Köpschall
    • 1
  • Karin Rohbock
    • 1
  • Ksenya Varakina
    • 1
  • Sandrine Verpoorten
    • 1
  • Thomas Reinbothe
    • 1
  • Thomas Schimmang
    • 2
  • Lukas Rüttiger
    • 1
  • Marlies Knipper
    • 1
  1. 1.Molecular Physiology of Hearing, Hearing Research Centre Tübingen (THRC), Department of OtolaryngologyUniversity of TübingenTübingenGermany
  2. 2.Instituto de Biología y Genética MolecularUniversidad de Valladolid y Consejo Superior de Investigaciones CientíficasValladolidSpain

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