Thursday, November 21, 2024
11/21/2024
Loss of hair-cell innervation by auditory-nerve fibers is a prevalent cochlear pathology in humans associated with aging and sound overexposure, that does not impact audiometric thresholds in quiet. Called cochlear synaptopathy, this inner-ear problem is widely expected to cause “hidden” hearing difficulties such as impaired speech perception in noise. However, evidence that synaptopathy causes hidden hearing loss remains controversial despite over a decade of intensifying research on the topic. Animal studies are well positioned to advance this field because the approach allows direct induction of synaptopathy and targeted neural recordings to identify underlying mechanisms. However, only a few studies have leveraged this approach. The proposed study will clarify specific aspects of perception impacted by synaptopathy and underlying mechanisms using animal behavioral experiments, auditory-nerve fiber recordings, and midbrain-neural recordings in actively behaving animals. Experiments are conducted in budgerigars (parakeet) based on adaptability of this species to operant-conditioning experiments and behavioral sensitivity similar to humans on many simple and complex hearing tasks. Furthermore, accumulating evidence highlights conserved auditory processing mechanisms between birds and mammals at peripheral and central levels. We test the novel hypothesis that synaptopathy impairs perception of brief acoustic cues due to amplification of neural onset responses, a nominal “gain of function” that we predict will degrade neural resolution of short signals due to response saturation. This hypothesis is a significant departure from conventional theories based on low spontaneous-rate fiber loss, which was not confirmed in a recent mouse study, and has direct relevance to speech communication for which auditory analysis of short time periods is often critical. Furthermore, the hypothesis is supported by recent auditory-nerve studies, and new preliminary data in budgerigars showing that synaptopathy selectively degrades detection of tone bursts presented at the onset of a noise masker. Synaptopathy is induced with kainic acid and validated histologically using established methodology. Additional Aim-1 studies extend behavioral experiments into the critical realm of speech using synthesized consonants. Aim-2 experiments use single-fiber auditory-nerve recordings to establish a firm baseline knowledge of how synaptopathy impacts peripheral encoding and temporal dynamics. Aim 3 uses neural recordings from a key midbrain processing center to determine the changes in central processing with synaptopathy; recordings from actively behaving animals are analyzed with neural decision-variable correlations for maximum insight into neural bases of normal and impaired perception. The detailed knowledge of specific perceptual deficits and underlying changes in peripheral/central encoding provided by this work will help guide the development of new public-health strategies to address cochlear synaptopathy. Ultimately, the proposed project holds promise to expand and potentially redefine current thinking on synaptopathy and hidden hearing loss.
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