Excitotoxic damage to auditory nerve afferents and spiral ganglion neurons is correlated with developmental upregulation of AMPA and KA receptors.

Abstract Excess release of glutamate at the inner hair cell-type I auditory nerve synapse results in excitotoxicity characterized by rapid swelling and disintegration of the afferent synapses, but in some cases, the damage expands to the spiral ganglion soma. Cochlear excitotoxic damage is largely mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and kainate receptor (KAR) and potentially N-methyl-D-aspartate receptors (NMDAR). Because these receptors are developmentally regulated, the pattern of excitotoxic damage could change during development. To test this hypothesis, we compared AMPAR, NMDAR and KAR immunolabeling and excitotoxic damage patterns in rat postnatal day 3 (P3) and adult cochlear cultures. At P3, AMPAR and KAR immunolabeling, but not NMDAR, was abundantly expressed on peripheral nerve terminals adjacent to IHCs. In contrast, AMPAR, KAR and NMDAR immunolabeling was minimal or undetectable on the SGN soma. In adult rats, however, AMPAR, KAR and NMDAR immunolabeling occurred on both peripheral nerve terminals near IHCs as well as the soma of SGNs. High doses of Glu and KA only damaged peripheral nerve terminals near IHCs, but not SGNs, at P3, consistent with selective expression of AMPAR and KAR expression on the terminals. However, in adults, Glu and KA damaged both peripheral nerve terminals near IHCs and SGNs both of which expressed AMPAR and KAR. These results indicate that cochlear excitotoxic damage is closely correlated with structures that express AMPAR and KAR.