# The Effect of Cochlear Synaptopathy on Auditory Nerve Responses in the Budgerigar

> **NIH NIH F31** · UNIVERSITY OF ROCHESTER · 2024 · $48,974

## Abstract

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).
Ulti...

## Key facts

- **NIH application ID:** 10994381
- **Project number:** 1F31DC021889-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Leslie Gonzales
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-04-16 → 2025-04-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994381

## Citation

> US National Institutes of Health, RePORTER application 10994381, The Effect of Cochlear Synaptopathy on Auditory Nerve Responses in the Budgerigar (1F31DC021889-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10994381. Licensed CC0.

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