Signaling through erbB receptors is a critical functional regulator in the mature cochlea

Authors

  • Futoshi Watanabe,

    1. Center for Hearing and Communication Research and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
    2. Department of Otolaryngology, Ehime University School of Medicine, Matsuyama, Japan
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    • *

      F.W. and M.K. contributed equally to this manuscript.

  • Mette Kirkegaard,

    1. Center for Hearing and Communication Research and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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    • *

      F.W. and M.K. contributed equally to this manuscript.

  • Suguru Matsumoto,

    1. Center for Hearing and Communication Research and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
    2. Department of Otolaryngology, Ehime University School of Medicine, Matsuyama, Japan
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  • Cecilia Gont,

    1. Center for Hearing and Communication Research and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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  • Paula Mannström,

    1. Center for Hearing and Communication Research and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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  • Mats Ulfendahl,

    1. Center for Hearing and Communication Research and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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  • Anders Fridberger

    1. Center for Hearing and Communication Research and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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Dr A. Fridberger, as above.
E-mail: anders.fridberger@ki.se

Abstract

Noise, ototoxic substances and various genetic factors are common causes of profound hearing loss. Cochlear implants can often restore hearing in these cases, but only if a sufficient number of responsive auditory nerve fibers remain. Over time, these nerve fibers degenerate in the damaged ear, and it is therefore important to establish factors that control neuronal survival and maintain neural excitability. Recent studies show that neuregulins and their receptors are important for survival and proper targeting of neurons in the developing inner ear. A role for neuregulins as maintainers of the neuronal population in the mature inner ear was therefore hypothesized. Here, this hypothesis was directly tested by chronic local application of substances that block neuregulin receptors. Using auditory brainstem response measurements, we demonstrate that such receptor block leads to a progressive hearing impairment that develops over the course of weeks. This impairment occurs despite a normal number of auditory neurons and preserved outer hair cell function. Real-time quantitative reverse transcriptase-polymerase chain reaction shows alterations in neurotrophin-3 expression, suggesting that this growth factor participates in regulating cochlear sensitivity. The present work demonstrates the critical importance of neuregulin/erbB signaling in long-term functional regulation in the mature guinea pig hearing organ.

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