# Cellular mechanisms of age related hearing loss

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $390,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Cochlear nucleus (CN) is the first neural station of the central auditory system that processes all sound
information from the auditory nerve (AN). Principal neurons of CN encode different aspects of sound,
including information about the temporal fine structure (TFS) that is essential for auditory tasks like sound
localization and speech detection in noisy environment. During age related hearing loss (ARHL), the central
processing of TFS information is compromised, leads to perceptual deficits. The overall hypothesis is that
modifications in CN neurons and neural circuits during aging contribute to the malfunction of auditory temporal
processing that underlies ARHL. The project investigates the cellular mechanisms of ARHL in CN bushy
neurons, which are specialized in processing TFS information, as well as their excitatory inputs from AN and
inhibitory inputs from CN interneurons during aging. Our previous studies showed that synaptopathy occurs at
AN central terminals during ARHL, specifically the endbulb of Held synapses, which show age related
degradation in transmitting auditory information to postsynaptic bushy neurons. The decrease in endbulb
function is due to compromised synaptic transmission that is associated with dysregulated calcium signaling at
the synaptic terminal. In Aim1, the project investigates the mechanisms of different calcium signaling
pathways during aging at the endbulb of Held synapse, including calcium uptake and removal, calcium influx
via voltage gated calcium channels, synaptic vesicle replenishment, as well as the expression of different
calcium sensors. Our prior study also found that bushy neurons are depolarized and more excitable during
aging. In Aim2, the project will test the hypothesis that auditory system enhances central gain in bushy
neurons to compensate for the weakened AN input during ARHL. Mechanisms of voltage-gated ion channels
during ARHL will be studied by quantifying membrane conductances that underlie neural excitability in bushy
neurons during aging. In Aim3, the project will elucidate the mechanisms of inhibition during ARHL by
investigating the effect of inhibition on firing property of bushy neurons, assessing synaptic strength of
glycinergic inputs, and evaluating the neural excitability of CN interneurons as well as their AN inputs during
aging. To achieve these goals, the project utilizes techniques including behavioral hearing test (auditory
brainstem response), whole-cell recording under current or voltage clamp mode using acute brain slices,
pharmacological manipulation, as well as immunohistochemistry, using CBA/CaJ mice as the animal model for
ARHL at ages up to 30 months. These studies will have a significant impact on our understanding of synaptic
and cellular mechanisms underlying ARHL, which is fundamental and essential for developing therapeutic
approaches to restore neural processing in the central auditory system and eventually reinstate sound
perceptio...

## Key facts

- **NIH application ID:** 9948619
- **Project number:** 5R01DC016037-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Ruili Xie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2017-09-19 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948619

## Citation

> US National Institutes of Health, RePORTER application 9948619, Cellular mechanisms of age related hearing loss (5R01DC016037-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948619. Licensed CC0.

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