The inner hair cell afferent/efferent synapses revisited: a basis for new therapeutic strategies.

Within the cochlea, the sensory inner hair cells, which transduce the mechanical displacement of the basilar membrane into neural activity, release glutamate that acts on postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor channels located on dendrites of primary auditory neurons. Up to now, it has been thought that the auditory nerve responses passively reflected the motion of the basilar membrane supporting the organ of Corti. Here, we show that dopaminergic lateral olivocochlear efferents drive a permanent gain control at the site of auditory action potential initialization. A dysfunction of this system leads to the development of early signs of excitotoxicity. With the knowledge of the molecular mechanisms involved at this first synaptic complex in the cochlea, it is now possible to envisage local treatments for spiral ganglion neurons, either to stop an excitotoxically induced hyperexcitability (probably the starting point of most posttraumatic tinnitus) or to prevent neuronal death (neural presbycusis).