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Regenerated Synapses Between Postnatal Hair Cells and Auditory Neurons

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Abstract

Regeneration of synaptic connections between hair cells and spiral ganglion neurons would be required to restore hearing after neural loss. Here we demonstrate by immunohistochemistry the appearance of afferent-like cochlear synapses in vitro after co-culture of de-afferented organ of Corti with spiral ganglion neurons from newborn mice. The glutamatergic synaptic complexes at the ribbon synapse of the inner hair cell contain markers for presynaptic ribbons and postsynaptic densities. We found postsynaptic density protein PSD-95 at the contacts between hair cells and spiral ganglion neurons in newly formed synapses in vitro. The postsynaptic proteins were directly facing the CtBP2-positive presynaptic ribbons of the hair cells. BDNF and NT-3 promoted afferent synaptogenesis in vitro. Direct juxtaposition of the postsynaptic densities with the components of the preexisting ribbon synapse indicated that growing fibers recognized components of the presynaptic sites. Initiation of cochlear synaptogenesis appeared to be influenced by glutamate release from the hair cell ribbons at the presynaptic site since the synaptic regeneration was impaired in glutamate vesicular transporter 3 mutant mice. These insights into cochlear synaptogenesis could be relevant to regenerative approaches for neural loss in the cochlea.

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Acknowledgements

We thank Robert Edwards and Rebecca Seal (University of California, San Francisco) for the VGLUT3 knockout mouse. This work was supported by grants from the National Institute on Deafness and other Communicative Disorders (RO1 DC007174 and P30 DC05209).

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Authors and Affiliations

  1. Department of Otology and Laryngology, Harvard Medical School, Boston, MA, 02115, USA

    Mingjie Tong, Aurore Brugeaud & Albert S. B. Edge

  2. Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA, 02114, USA

    Mingjie Tong, Aurore Brugeaud & Albert S. B. Edge

  3. Program in Speech and Hearing Bioscience and Technology, Division of Health Science and Technology, Harvard and MIT, Cambridge, MA, 02139, USA

    Albert S. B. Edge

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  1. Mingjie Tong
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  2. Aurore Brugeaud
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Correspondence to Albert S. B. Edge.

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Tong, M., Brugeaud, A. & Edge, A.S.B. Regenerated Synapses Between Postnatal Hair Cells and Auditory Neurons. JARO 14, 321–329 (2013). https://doi.org/10.1007/s10162-013-0374-3

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  • DOI: https://doi.org/10.1007/s10162-013-0374-3

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