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

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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 CreER^T 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.

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Guoqiang Wan

Boston Children's Hospital, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Maria E Gómez-Casati

Boston Children's Hospital, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Angelica R Gigliello

Boston Children's Hospital, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Charles Liberman

Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Gabriel Corfas

University of Michigan, Ann Arbor, United States

For correspondence
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.

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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.