Spatial patterns of noise-induced inner hair cell ribbon loss in the mouse mid-cochlea

In the mammalian cochlea, moderate acoustic overexposure leads to loss of ribbon -type synapse between the inner hair cell (IHC) and its postsynaptic spiral ganglion neuron (SGN), causing a reduced dynamic range of hearing but not a permanent threshold elevation. A prevailing view is that such ribbon loss (known as synaptopathy) selectively impacts the low -spontaneous -rate and high -threshold SGN fibers contacting predominantly the modiolar IHC face. However, the spatial pattern of synaptopathy remains scarcely characterized in the most sensitive mid -cochlear region, where two morphological subtypes of IHC 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 IHC subtypes differ in the worst -hit area of synaptopathy. Moreover, we show relative enrichment of mitochondria in the surviving SGN terminals, providing key experimental evidence for the longproposed role of SGN-terminal mitochondria in synaptic vulnerability.