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Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma

  1. Guoqiang Wan
  2. Maria E Gómez-Casati
  3. Angelica R Gigliello
  4. Charles Liberman
  5. Gabriel Corfas Is a corresponding author
  1. Boston Children's Hospital, United States
  2. Harvard Medical School, United States
  3. University of Michigan, United States
Research Article
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Cite as: eLife 2014;3:e03564 doi: 10.7554/eLife.03564

Abstract

Neurotrophin-3 (Ntf3) and brain derived neurotrophic factor (Bdnf) are critical for sensory neuron survival and the establishment of neuronal projections to sensory epithelia in the embryonic inner ear, but their postnatal functions remain poorly understood. Using cell-specific inducible gene recombination in mice we found that, in the postnatal inner ear, Bbnf and Ntf3 are required for the formation and maintenance of hair cell ribbon synapses in the vestibular and cochlear epithelia, respectively. We also show that supporting cells in these epithelia are the key endogenous source of the neurotrophins. Using a new hair cell CreERT line with mosaic expression, we also found that Ntf3's effect on cochlear synaptogenesis is highly localized. Moreover, supporting cell-derived Ntf3, but not Bbnf, promoted recovery of cochlear function and ribbon synapse regeneration after acoustic trauma. These results indicate that glial-derived neurotrophins play critical roles in inner ear synapse density and synaptic regeneration after injury.

Article and author information

Author details

  1. Guoqiang Wan

    1. Boston Children's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Maria E Gómez-Casati

    1. Boston Children's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Angelica R Gigliello

    1. Boston Children's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Charles Liberman

    1. Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Gabriel Corfas

    1. University of Michigan, Ann Arbor, United States
    For correspondence
    1. corfas@med.umich.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to the approved institutional animal care and use committee (IACUC) protocol (#11-03-1911R) of Children's Hospital Boston.

Reviewing Editor

  1. Freda Miller, Reviewing Editor, The Hospital for Sick Children Research Institute, University of Toronto, Canada

Publication history

  1. Received: June 3, 2014
  2. Accepted: October 9, 2014
  3. Accepted Manuscript published: October 20, 2014 (version 1)
  4. Version of Record published: November 11, 2014 (version 2)

Copyright

© 2014, Wan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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