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

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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.

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Acknowledgments

This work was supported by the Marie Curie Research Training Network CavNET MRTN-CT-2006-035367, Deutsche Forschungsgemeinschaft DFG-Kni-316-4-1, and Hahn Stiftung (Index AG).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Molecular Physiology of Hearing, Hearing Research Centre Tübingen (THRC), Department of Otolaryngology, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany

    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, Lukas Rüttiger & Marlies Knipper

  2. Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, C/Sanz y Forés 3, 47003, Valladolid, Spain

    Thomas Schimmang

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  1. Wibke Singer
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Corresponding authors

Correspondence to Lukas Rüttiger or Marlies Knipper.

Additional information

Wibke Singer and Annalisa Zuccotti equally contributed to this work.

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Singer, W., Zuccotti, A., Jaumann, M. et al. Noise-Induced Inner Hair Cell Ribbon Loss Disturbs Central Arc Mobilization: A Novel Molecular Paradigm for Understanding Tinnitus. Mol Neurobiol 47, 261–279 (2013). https://doi.org/10.1007/s12035-012-8372-8

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  • DOI: https://doi.org/10.1007/s12035-012-8372-8

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