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.

Juan Hong,Peidong Dai,Jieying Li,Yanping Zhang,Lusen Shi,Huawei Li,Lin Yang,Liujie Ren,Tianyu Zhang,Ao Li,Yan Chen

doi:10.1155/2018/3989201

Juan Hong, Peidong Dai + Show 9 more

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https://doi.org/10.1155/2018/3989201

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Cochlear inner hair cell (IHC) ribbon synapses play an important role in sound encoding and neurotransmitter release. Previous reports show that both noise and aminoglycoside exposures lead to reduced numbers and morphologic changes of synaptic ribbons. In this work, we determined the distribution of N-methyl-D-aspartate receptors (NMDARs) and their role in the gentamicin-induced pathological changes of cochlear IHC ribbon synaptic elements. In normal mature mouse cochleae, the majority of NMDARs were distributed on the modiolar side of IHCs and close to the IHC nuclei region, while most of synaptic ribbons and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) were located on neural terminals closer to the IHC basal poles. After gentamicin exposure, the NMDARs increased and moved towards the IHC basal poles. At the same time, synaptic ribbons and AMPARs moved toward the IHC bundle poles on the afferent dendrites. The number of ribbon synapse decreased, and this was accompanied by increased auditory brainstem response thresholds and reduced wave I amplitudes. NMDAR antagonist MK801 treatment reduced the gentamicin-induced hearing loss and the pathological changes of IHC ribbon synapse, suggesting that NMDARs were involved in gentamicin-induced ototoxicity by regulating the number and distribution of IHC ribbon synapses.

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Cochlear inner hair cell (IHC) ribbon synapses play an important role in sound encoding and glutamate release
GluN1 and GluA2 were used as markers of N-methyl-D-aspartate receptors (NMDARs) and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), respectively
Gentamicin groups, resp.) (Figure 4(f) and Supplementary Table 1). These results indicate that there was a significant decrease in the number of presynaptic ribbons and postsynaptic AMPARs at the basal poles of the IHCs (Figures 4(e)–4(g)), and the number of ribbon synaptic pairs significantly decreased at the basal poles of the IHCs in the gentamicin-treated group compared with the control group (p < 0 05) (Figure 4(g))

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Introduction

Cochlear inner hair cell (IHC) ribbon synapses play an important role in sound encoding and glutamate release. The IHC ribbon synapses are the first afferent synaptic connection in the hearing pathway, and they are located between the IHCs and the terminals of spiral ganglion neurons (SGNs). Bursts of synaptic activity are induced through periodic excitation of IHCs by mechanisms that are intrinsic to the cochlea [1], resulting in IHC Ca2+ spikes, glutamate release, and bursts of action potentials in SGNs that are carried to the brain by auditory nerve fibers. Liu et al found that moderate ototoxicity in mice leads to reduced numbers and morphologic changes in the synaptic ribbons, which are accompanied by mild hearing loss but no significant loss of HCs or SGNs in the cochlea [8]. The mechanism behind these pathological changes in cochlear IHC ribbon synapse remains unclear

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