Protection of cochlear synapses from noise-induced excitotoxic trauma by blockade of Ca ²⁺ -permeable AMPA receptors

Significance Noise can cause excitotoxic trauma to cochlear synapses by triggering excessive release of the neurotransmitter glutamate from the auditory sensory hair cells. We report that a specific class of glutamate receptors, Ca 2+ -permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (CP-AMPARs), is largely responsible for this trauma. Because cochlear synapses are heterogenous with respect to glutamate receptors, the observation that a specific class is responsible might explain the variability in susceptibility to noise among synapses. Selective blockade of CP-AMPARs prevents excitotoxicity and noise-induced cochlear synaptopathy, while other glutamate receptors continue to mediate neurotransmission and allow hearing.