# Age-dependent plasticity of central auditory synapses

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2024 · $294,475

## Abstract

PROJECT SUMMARY/ABSTRACT
 Age-related hearing loss (ARHL) is one of the most prevalent health conditions in the elderly. Structural
degradation and functional decline in the peripheral and central auditory systems underlie the gradual loss of
perception with age. In particular, recent findings suggest that preferential damage of selective subtypes of spiral
ganglion neurons (SGNs) precedes overt hearing loss. It remains unclear how age-related SGN changes link to
structural and physiological alterations in the central auditory system in contributing to the development of ARHL.
The cochlear nucleus (CN) is the only target for all SGNs and represents the starting site of central auditory
processing. This role emphasizes that understanding changes in structure and function of the CN during aging
is essential to elucidate the mechanisms of ARHL. Our overall hypothesis is that age-dependent changes in the
cochlea results in alterations in the CN circuit that impact the signal processing of the entire central auditory
system. This study of the CN aims to identify age-related plastic alterations in auditory nerve (AN) synapses and
their excitatory and inhibitory CN targets to determine the synaptic and cellular mechanisms of ARHL in the CN.
Aim 1 will determine the age-dependent changes in the physiology and morphology of different subtypes
of AN synapses during ARHL. We will combine electrophysiology and immunohistochemistry to identify three
subtypes of AN synapses based on the expression of different SGN molecular markers and determine these
synapses' electrophysiological property and morphological features in acute CN slices from different age groups
of genetically modified mice. Aim 2 will identify the age-related changes in the physiology and cellular
morphology of CN principal neurons during ARHL. We hypothesize that CN principal bushy neurons with
different subtypes of AN synaptic input are differentially modified with age in physiology and morphology,
resulting in compromised spike output during ARHL. We will determine the age-related changes among different
bushy neurons in intrinsic properties, spike output, potassium conductances, and cellular morphology in
conjunction with specific subtypes of AN input they receive. Aim3 will elucidate the mechanisms of weakened
inhibition in the CN during ARHL. We will test the hypothesis that inhibitory D-stellate neurons are innervated
mainly by low spontaneous rate/high threshold SGNs whose selective loss with age results in reduced output
and weakened inhibition in the CN. This mechanism of inhibition will be further tested by ablating specific SGN
subtypes in pharmacogenetic mice at different ages. Our studies will identify age-related changes in the CN
circuit, and in conjunction with selective alterations of SGN subtypes (Project 1), to determine the affected AN
synapses and their impact on the output of CN principal and local inhibitory neurons.

## Key facts

- **NIH application ID:** 10910246
- **Project number:** 7P01AG051443-07
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Ruili Xie
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $294,475
- **Award type:** 7
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910246

## Citation

> US National Institutes of Health, RePORTER application 10910246, Age-dependent plasticity of central auditory synapses (7P01AG051443-07). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10910246. Licensed CC0.

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