Selective Vulnerability of Spiral Ganglion Neuronal Subtypes to Noise-Induced Synaptopathy in the Cochlea

Abstract

We are bombarded with noise in our daily environment from the moment we wake up to a blasting alarm clock to the TV we may unwind to at the end of the night. This constant assault to our ears has both acute and chronic consequences. While seemingly harmless, moderate but prolonged noise exposures are sufficient to damage the synapse between sensory hair cells (IHCs) and their postsynaptic Spiral Ganglion Neurons (SGNs). This type of sensorineural hearing loss (SNHL) is marked by difficulty with complex auditory tasks such as detecting speech in a noisy restaurant, despite normal detection thresholds. Physiological and anatomical studies of noise-induced synaptopathy point to a subset of SGNs with the highest threshold as the primary target of acoustic trauma (AT). Due to the dynamic changes that are known to occur at the IHC-SGN synapses in response to AT, these methods are limited in their ability to confidently assign SGNs to their respective subpopulations post-exposure. To definitively determine whether there is differential vulnerability of SGN subtypes to noise, we used 3 separate transgenic mouse lines to molecularly label SGN subtypes: Netring1Cre;Ai14 to label high- and medium-threshold SGNs, the Calb2CreERT2 mouse line to label low- and medium-thresholds SGNs, and Lypd1CreERT2 to label high-threshold SGNs. After comparing noise-induced synaptopathy associated with labeled SGNs across these 3 lines, we were able to confirm the selective vulnerability of synapses of high-threshold SGNs, as predicted by previous studies. Next, we wanted to determine whether a shift in the molecular identity of these more vulnerable SGNs to that of the more resilient low threshold SGNs via the conditional knock-out of Runx1 offers protection from noise-induced synaptopathy. We found that Runx1CKO mice had similar threshold shifts to controls after AT but retained more synapses per HC at high frequencies. Here, we show that low threshold SGNs are more resilient to AT and the expansion of this subpopulation may have a protective effect.