The synapses between the inner hair cells (IHCs) and the radial auditory dendrites are thought to be glutamatergic. Besides its fast excitatory properties,
glutamate is known to be neurotoxic when released in excess or incompletely recycled. In the cochlea, this may occur in two pathological conditions:
ischemia and noise
trauma. We have further investigated the acute excitotoxicity (i.e. the swelling of type I afferent dendrites) by electron microscopy processing on guinea pig cochleas after an ischemic exposure lasting 5 to 40 min. The radial auditory dendrites reacted to
ischemia in a time-dependent manner, with the swelling extending when the duration of
ischemia increased. The type and the specificity of swelling were comparable to what acutely occurs after an exposure to
glutamate analogs such as
kainic acid or
AMPA. A protection against this swelling was obtained by perfusing the cochlea with
glutamate antagonists prior to
ischemia.
DNQX, an antagonist at
AMPA/
kainate receptors, had a powerful protective effect, and almost complete protection was obtained by perfusing both
DNQX and D-AP5 (a
NMDA antagonist). The latter results indicate that the two classes of
glutamate receptors (
AMPA/
kainate and
NMDA), both found to be electrophysiologically active at the IHC-auditory nerve synapse, are also involved in the excitotoxic processes. In addition, we also report data involving
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 findings constitute a promising pharmacological approach of cochlear pathologies such as neural
presbycusis.