Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice.

Hongchao Liu,Pengcheng Xu,Longhao Wang,Zhaoyan Wang,Hao Wu,Hu Peng,Huihui Liu

doi:10.3389/fcell.2020.635201

Abstract

Noise exposure of a short period at a moderate level can produce permanent cochlear synaptopathy without seeing lasting changes in audiometric threshold. However, due to the species differences in inner hair cell (IHC) calcium current that we have recently discovered, the susceptibility to noise exposure may vary, thereby impact outcomes of noise exposure. In this study, we investigate the consequences of noise exposure in the two commonly used animal models in hearing research, CBA/CaJ (CBA) and C57BL/6J (B6) mice, focusing on the functional changes of cochlear IHCs. In the CBA mice, moderate noise exposure resulted in a typical fully recovered audiometric threshold but a reduced wave I amplitude of auditory brainstem responses. In contrast, both auditory brainstem response threshold and wave I amplitude fully recovered in B6 mice at 2 weeks after noise exposure. Confocal microscopy observations found that ribbon synapses of IHCs recovered in B6 mice but not in CBA mice. To further characterize the molecular mechanism underlying these different phenotypes in synaptopathy, we compared the ratio of Bax/Bcl-2 with the expression of cytochrome-C and found increased activity in CBA mice after noise exposure. Under whole-cell patch clamped IHCs, we acquired two-photon calcium imaging around the active zone to evaluate the Ca2+ clearance rate and found that CBA mice have a slower calcium clearance rate. Our results indicated that excessive accumulation of calcium due to acoustic overexposure and slow clearance around the presynaptic ribbon might lead to disruption of calcium homeostasis, followed by mitochondrial dysfunction of IHCs that cause susceptibility of noise-induced cochlear synaptopathy in CBA mice.

Highlights

Hearing loss is one of the most common health problems that affects communication and impacts life quality (Lin et al, 2011)
Our experiments have revealed that excessive accumulation due to slow clearance of calcium around the presynaptic ribbon during acoustic overexposure may lead to disruption of calcium homeostasis, followed by mitochondrial dysfunction of inner hair cell (IHC) that cause susceptibility of noise-induced cochlear synaptopathy in CBA mice
Analysis of auditory brainstem responses (ABRs) wave I amplitude revealed that CBA mice exhibited a significant reduction of wave I amplitude reduction at 14 days after noise exposure at high sound pressure level (SPL) starting from 80 dB

Summary

Introduction

Hearing loss is one of the most common health problems that affects communication and impacts life quality (Lin et al, 2011). The inner hair cell (IHC) and spiral ganglion neuron (SGN) synapse, both pre- and postsynaptic structures, are vulnerable to noise exposure (Kujawa and Liberman, 2015; Liu et al, 2019b; Michanski et al, 2019) This cochlear synaptopathy is an “auditory processing disorder” that alters auditory information processing and leads to difficulties in speech discrimination in noisy environments (Shi et al, 2016). Presynaptic-Ca2+ influx through voltage-gated Ca2+ channels initiates mitochondrialCa2+ uptake around the ribbons and subsequent mitochondrial damage (Wong et al, 2019) Based on such a notion, this study further analyzes the functional alterations of IHC ribbon synapses after one episode of noise exposure and explore possible mechanisms in functional differences between B6 and CBA mice

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Conclusion