Summary: | <p>Normal audiometric thresholds following noise exposure have generally been considered as an indication of a recovered cochlea and intact peripheral auditory system, yet recent animal work has challenged this classic assumption. Moderately noise-exposed animals have been shown to have permanent loss of synapses on inner hair cells (IHCs) and permanent damage to auditory nerve fibers (ANFs), specifically the low-spontaneous rate fibers (low-SR), despite normal electrophysiological thresholds. Loss of cochlear synapses, known as cochlear synaptopathy, disrupts auditory-nerve signaling, which may result in perceptual speech deficits in noise despite normal audiometric thresholds. Perceptual deficit studies in humans have shown evidence consistent with the idea of cochlear synaptopathy. To date, there has been no direct evidence linking cochlear synaptopathy and perceptual deficits. Our research aims to develop a cochlear synaptopathy model in chinchilla, similar to previously established mouse and guinea pig models, to provide a model in which the effects of cochlear synaptopathy on behavioral and physiological measures of low-frequency temporal coding can be explored. </p><p> Positive-reinforcement operant-conditioning was used to train animals to perform auditory detection behavioral tasks for four frequencies: 0.5, 1, 2, and 4 kHz. Our goal was to evaluate the detection abilities of chinchillas for tone-in-noise and sinusoidal amplitude modulated (SAM) tone behavioral tasks, which are tasks thought to rely on low-SR ANFs for encoding. Testing was performed before and after exposure to an octave-band noise exposure centered at 1 kHz for 2 hours at 98.5 dB SPL. This noise exposure produced the synaptopathy phenotype in naïve chinchillas, based on auditory-brainstem responses (ABRs), otoacoustic emissions (OAEs) and histological analyses. Threshold shift and inferred synaptopathy was determined from ABR and OAE measures in our behavioral animals. </p><p> Overall, we have shown that chinchillas, similar to mice and guinea pigs, can display cochlear synaptopathy phenotype following moderate-level sound exposure. This finding was seen in naïve exposed chinchillas, but our results suggest the susceptibility to noise can vary between naïve and behavioral cohorts because minimal physiological evidence for synaptopathy was observed in the behavioral group. Hearing sensitivity determined by a tone-in-quiet behavioral task on normal hearing chinchillas followed trends reported previously, and supported the lack of permanent threshold shift following moderate noise exposure. As we expected, thresholds determined in a tone-in-noise behavioral task were higher than thresholds measured in quiet. Behavioral thresholds measured in noise after moderate noise exposure did not show threshold shifts relative to pre-exposure thresholds in noise. As expected, chinchillas were more sensitive at detecting fully modulated SAM-tone signals than less modulated, with individual modulation depth thresholds falling within previously reported mammalian ranges. </p><p> Although we have only been able to confirm cochlear synaptopathy in pilot assays with naïve animals so far (i.e., not in the pilot behavioral animals), this project has developed an awake protocol for moderate-level noise exposure, an extension to our lab’s previous experience with high-level permanent damage noise exposure under anesthesia. Also, we successfully established chinchilla behavioral training and testing protocols on several auditory tasks, a new methodology to our laboratory, which we hope will ultimately allow us to identify changes in auditory perception resulting from moderate-level noise exposure. </p>
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