Abstract
Hearing is an extremely delicate sense that is particularly vulnerable to insults from environment, including drugs and noise. Unsurprisingly, mice of different genetic backgrounds show different susceptibility to hearing loss. In particular, CBA/CaJ (CBA) mice maintain relatively stable hearing over age while C57BL/6J (B6) mice show a steady decline of hearing, making them a popular model for early onset hearing loss. To reveal possible underlying mechanisms, we examined cellular differences in the cochlea of these two mouse strains. Although the ABR threshold and Wave I latency are comparable between them, B6 mice have a smaller Wave I amplitude. This difference is probably due to fewer spiral ganglion neurons found in B6 mice, as the number of ribbon synapses per inner hair cell (IHC) is comparable between the two mouse strains. Next, we compared the outer hair cell (OHC) function and we found OHCs from B6 mice are larger in size but the prestin density is similar among them, consistent with the finding that they share similar hearing thresholds. Lastly, we examined the IHC function and we found IHCs from B6 mice have a larger Ca2+ current, release more synaptic vesicles and recycle synaptic vesicles more quickly. Taken together, our results suggest that excessive exocytosis from IHCs in B6 mice may raise the probability of glutamate toxicity in ribbon synapses, which could accumulate over time and eventually lead to early onset hearing loss.
Highlights
The dysfunction and/or loss of sensorineural cells in cochlea often result in hearing impairment, which is a major social and health problem worldwide (Fujimoto et al, 2017)
We found that inner hair cells (IHCs) from B6 mice release more synaptic vesicles for both short and long step stimulations, suggesting that IHCs from these mice have a larger readily releasable pool (RRP) and replenish synaptic vesicles more quickly
When we applied doublepulse stimulation, we found that exocytosis from B6 IHCs recovers more quickly, which is probably due to the greater Ca2+ influx (Babai et al, 2010)
Summary
The dysfunction and/or loss of sensorineural cells in cochlea often result in hearing impairment, which is a major social and health problem worldwide (Fujimoto et al, 2017). SGNs are the first order of spike-generating neurons in the auditory pathway, and they connect hair cells to neurons in cochlear nuclei in the brainstem. Both of them are prone to be damaged by multiple and complex underlying etiologies, such as aging, acoustic exposure, ototoxic drugs, genetic disorders, etc. Exploring possible mechanisms of Hearing in CBA and B6 Mice sensorineural cell dysfunction will expand our understanding of neural and molecular basis of this sensory deficit
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