Impacts of cochlear synaptopathy on temporal dynamics of auditory neural responses in the budgerigar

Loss of synapses between the inner hair cell and auditory-nerve (AN) fibers, called cochlear synaptopathy, is a common health problem associated with aging and overexposure to loud sound. Cochlear synaptopathy is widely expected to cause hearing difficulties, while mixed evidence has been found. The budgerigar, a speech-mimicking parakeet species with sensitive low-frequency hearing and human-like auditory perception, is well-suited for auditory study given similar neuroarchitecture between birds and mammals. Cochlear synaptopathy may alter neural temporal dynamics (i.e. neural adaptation) along the ascending pathway, potentially leading to perceptual hearing difficulties in complex listening environments. To test this hypothesis, we used intracochlear injection of a glutamate analog, kainic acid (KA), to induce selective damage of AN fibers. The KA-induced AN damage was validated histologically and physiologically, and the hair cell epithelium was demonstrated to remain unaffected. A novel stimulus paradigm, the Poisson click train, was developed for fast assessment of neural adaptation. Adaptation at different processing stages along the ascending pathway was estimated using waves of the auditory brainstem response (ABR) generated by AN, midbrain and auditory cortex, then compared within individual animals before and after KA-exposure. Following cochlear synaptopathy, response patterns associated with stronger neural adaptation were found at conversational levels (65 dB SPL) in the AN. The midbrain-level waves had longer latency and more pronounced changes in adaptation than AN fibers, potentially due to cascading effects of cochlear synaptopathy. To further understand the perceptual consequences related to altered temporal dynamics, we examined the midbrain neural cues underlying behavioral detection of tone-in-noise stimuli with different temporal features in control animals. Neural responses from the auditory midbrain were recorded in awake budgerigars, and the neural thresholds were compared to behavioral thresholds obtained by operant conditioning tests. Specifically for transient signals in noise, behavioral detection was found to be correlated with the temporal profile of midbrain neural responses. Our findings demonstrate that cochlear synaptopathy alters the temporal dynamics of neural responses along the ascending auditory pathway. This alteration likely impacts neural processing of transient communication signals and might contribute to degraded real-world hearing abilities in people with cochlear synaptopathy.