PATHOPHYSIOLOGY OF THE GLUTAMATERGIC SYNAPSES IN THE COCHLEA

The synapses between the inner hair cells (IHCs) and the radial audito ry dendrites are thought to be glutamatergic. Besides its fast excitat ory properties, glutamate is known to be neurotoxic when released in e xcess or incompletely recycled. In the cochlea, this may occur in two pathological conditions: ischemia and noise trauma. We have further in vestigated the acute excitotoxicity (i.e. the swelling of type I affer ent dendrites) by electron microscopy processing on guinea pig cochlea s after an ischemic exposure lasting 5 to 40 min. The radial auditory dendrites reacted to ischemia in a time-dependent manner, with the swe lling extending when the duration of ischemia increased. The type and the specificity of swelling were comparable to what acutely occurs aft er an exposure to glutamate analogs such as kainic acid or AMPA. A pro tection against this swelling was obtained by perfusing the cochlea wi th glutamate antagonists prior to ischemia. DNQX, an antagonist at AMP A/kainate receptors, had a powerful protective effect, and almost comp lete protection was obtained by perfusing both DNQX and D-AP5 (a NMDA antagonist). The latter results indicate that the two classes of gluta mate receptors (AMPA/kainate and NMDA), both found to be electrophysio logically active at the IHC-auditory nerve synapse, are also involved in the excitotoxic processes. In addition, we also report data involvi ng dopamine (its D2 agonist piribedil) a putative neurotransmitter at the lateral efferent synapses, in a postsynaptic protection of primary auditory neurons during transient ischemia. Altogether, these finding s constitute a promising pharmacological approach of cochlear patholog ies such as neural presbycusis.