N-Methyl-D-Aspartate Receptors Involvement in the Gentamicin-Induced Hearing Loss and Pathological Changes of Ribbon Synapse in the Mouse Cochlear Inner Hair Cells

Figure 9

Diagrams illustrating the gentamicin-induced changes in ribbons, NMDARs, and AMPARs at the IHC-SGN synapse in the mouse cochlea. (a) In the normal mouse adult cochlea, presynaptic ribbons and postsynaptic AMPARs show a nearly one-to-one relationship. The ribbon synaptic pairs (double staining for CtBP2-positive puncta and GluA2-positive patches) are distributed around the basal poles of the IHCs. Most of the AMPARs are observed in the ISBs, but most NMDARs are distributed on the neural dendritic terminals between the adjoining IHCs and closer to the IHC nuclei region. In IHC nuclei region, some NMDARs colocalize with GluA2-positive AMPAR puncta, which are smaller than AMPAR patches in the IHC basal pole region. In the mouse cochlea, each IHC is contacted by roughly 10–20 ANFs depending on cochlear location. Each cochlear neuron is excited by a single ribbon synapse with a single IHC. (b) After gentamicin treatment, AMPARs and NMDARs are relocated at nerve fiber terminals around IHCs, and their locations are essentially reversed. AMPARs move upwards towards the bundle poles of the IHCs, and NMDARs migrate downwards towards the basal poles of the IHCs. The number of colocalized AMPARs and NMDARs gradually increases in the IHC basal pole region. Some anomalously aggregated ribbons and/or AMPARs in the IHC basal pole region are observed. IHC: inner hair cell; SGN: spiral ganglion neuron; ISBs: inner spiral bundles; ANFs: afferent nerve fibers.

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