Noise-induced Synaptopathy Impacts the Long and Short Sensory Hair Cells Differently in the Mammalian Cochlea

In the mammalian cochlea, moderate acoustic overexposure leads to irreversible loss of ribbon-type synapse between sensory inner hair cell (IHC) and its postsynaptic auditory nerve fiber (ANF), causing a reduced dynamic range of hearing but not a permanently-elevated threshold. A prevailing view is that such ribbon loss (known as synaptopathy) selectively impacts those low-spontaneous-rate and high-threshold ANFs contacting predominantly the modiolar face of IHCs. However, the spatial pattern of synaptopathy remains scarce in the most sensitive mid-cochlear region, where long and short IHCs with distinct ribbon size gradients coexist. Here, we used volume electron microscopy to investigate noise exposure-related changes in the mouse IHCs with and without ribbon loss. Our quantifications reveal that the worst-hit areas of synaptopathy are the modiolar face of long IHCs and the pillar face of short IHCs. Moreover, we show relative enrichment of mitochondrial content in the survived ANF terminals, providing key experimental evidence for the long-proposed role of postsynaptic mitochondria in selective ribbon synapse degeneration following noise insult. ### Competing Interest Statement The authors have declared no competing interest.