Regenerated Synapses Between Postnatal Hair Cells and Auditory Neurons
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JARO 14: 321–329 (2013) DOI: 10.1007/s10162-013-0374-3 D 2013 Association for Research in Otolaryngology
Research Article
Journal of the Association for Research in Otolaryngology
Regenerated Synapses Between Postnatal Hair Cells and Auditory Neurons MINGJIE TONG,1,2 AURORE BRUGEAUD,1,2
AND
ALBERT S. B. EDGE1,2,3
1
Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA
2
Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA
3
Program in Speech and Hearing Bioscience and Technology, Division of Health Science and Technology, Harvard and MIT, Cambridge, MA 02139, USA Received: 26 August 2012; Accepted: 29 January 2013; Online publication: 20 February 2013
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.
Correspondence to: Albert S. B. Edge & Eaton-Peabody Laboratory & Massachusetts Eye and Ear Infirmary & 243 Charles Street, Boston, MA 02114, USA. Telephone: +1-617-5734452; fax: +1-617-7204408; [email protected]
Keywords: synaptic regeneration, auditory neurons, hair cells, VGLUT3, neurotrophins
INTRODUCTION Sound inputs are converted into electrical signals by cochlear hair cells (HCs), the sensory cells of the organ of Corti in the inner ear, and conveyed to the central auditory system by spiral ganglion neurons (SGNs), representing the first step of the ascending auditory pathway from the cochlea (Fuchs et al. 2003; Weisz et al. 2009). After excessive exposure to noise, both HCs and SGNs can be damaged (Liberman and Kiang 1978; Harding et al. 2002; Kujawa and Liberman 2009). Despite the capacity of peripheral neurons to regenerate, SGNs in mammals do not spontaneously recover from injury (Starr et al. 1996; White et al. 2000; McFadden et al. 20
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