The Effect of Cochlear Synaptopathy on Auditory Nerve Responses in the Budgerigar - As humans age it is common to lose afferent synapses between hair cells and auditory-nerve fibers (ANFs), known as cochlear synaptopathy (CS). While some studies have found that CS produces an associated impairment in the perception of complex sounds in noise (i.e., hidden hearing loss; HHL), others have seen no effect. Greater clarity into HHL requires a knowledge of CS effects on neural encoding in surviving ANFs, but these remain controversial due to few existing studies and conflicting results across investigations. Therefore, the first aim of the current study is to quantify the effects of CS on ANF response properties in a new animal model, the budgerigar (parakeet). One strength of using the budgerigar is their ability to hear the lower frequencies humans rely on for speech comprehension. Furthermore, the budgerigar is widely used in behavioral auditory research, including ongoing behavioral studies of CS in our lab, and shows performance comparable to humans for various complex auditory-discrimination tasks. Intracochlear infusions of 1-mM kainic acid, a glutamate analog, are performed to produce substantial ANF loss while sparing hair cells. We hypothesize that ANF responses in normal-hearing budgerigars will be fundamentally similar to other avians and mammals, including the dynamic range of rate-level functions, threshold distribution pattern, and similar tuning curves. Differences of interest include the number of ribbons per synapse, which could influence the statistics of spontaneous activity and the shape of rate-level functions. We hypothesize that CS will increase onset synchrony of single-fiber responses, based on recent discoveries in mouse and gerbil pointing to altered temporal dynamics of hair-cell ribbon synapses. We expect no other major changes with CS in other ANF response properties (e.g., dynamic range). Histological studies will test for synaptic changes. The second aim of the study is to develop tools for detecting CS. Despite its prevalence in humans, there are no sufficient non- invasive tools to detect CS. The envelope-following response (EFR) is a scalp potential evoked with amplitude- modulated stimuli, that may be more sensitive to CS in humans due to its relatively high amplitude. EFRs are typically measured using sinusoidally amplitude-modulated (SAM) tones, but a recent modeling study suggests that square-wave modulated (SWM) tones might provide more synchronous ANF responses and therefore may be more sensitive to detect CS. Hence, the current study will probe EFRs to SAM and SWM tones in animals before and after inducing CS. Preliminary data in the budgerigar demonstrate that EFRs evoked by SWM stimuli provide a stronger indication of histologically validated ANF damage in CS budgerigars than SAM EFRs. Finally, ANF responses to SAM and SWM tones will be recorded in control and CS ears to test for the hypothesized increase in synchrony to the modulation frequency for SWM tones (expected in both groups). Ultimately, the proposed experiments will characterize changes in ANF response properties following CS and develop non-invasive methods for this common cochlear pathology.
