# Molecular and Functional Mechanisms of the aging auditory neuron

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2024 · $513,400

## Abstract

Abstract
 During development, cochlear hair cells (HCs) and neurons must be wired correctly, qualitatively, and
quantitatively. These include specific auditory afferent neurons (AN) wired to the brainstem cochlear nuclei (CN).
The activity of HCs maintains the number, size, and functions of ANs. Previous studies suggest that aging may
result in preferential loss of specific AN subtypes.
 We hypothesize that ARHL arises from a loss of ultrafast afferent responses, accompanied by remodeling of
central auditory circuits and functions—changes that result in deficiencies in phase-locked response functions
in older adults.
 We propose to examine age-related changes in distinct AN using three knockin mouse models: calretinin
(Calb2)-eGFP, calbindin (Calb1)-mCherry, Pou4f1 and (brn3a)-CFP, and optogenetic and pharmacogenetic
mouse models. The work will focus on longitudinal changes in:
 1) structural (anatomic) projections from HCs to the brainstem nuclei (CN),
 2) afferent neuron subtype distributions and functions, and
 3) Identify the age dependence of ionic conductances in AN afferents
Aim 1 will trace afferent neuron subtype-specific projections from the cochlea to the CN and determine the age-
dependent changes to identify potential anatomic plasticity. We will measure age-dependent auditory function,
auditory brainstem responses (ABR), and distortion product otoacoustic emissions (DPOAE). We will evaluate
and perform these studies in parallel with changes in age-related auditory phenotype. For Aim 2, we will
determine regional and afferent neuron subtype variations in the response properties and the age-dependent
changes. We will evaluate the regularity of inter-spike intervals, synchronization parameters, including vector
strength (VS), winding ratio (k), and sensitivity to current injection, using experimental and physiological
stimulation. Finally, for Aim 3, we will identify the age dependence of ionic conductances in three groups of
afferent neurons. We will use patch-clamp analyses of the kinetics, voltage-dependence, pharmacology, and
conductance in young and aged neurons to determine the underlying mechanisms for the differences in response
properties of three neuronal subtypes, using computational analyses.
Thus, we will address the complexity of anatomic projections and signal processing and subsequent age-
dependent changes, which are necessary for developing a treatment for ARHL.

## Key facts

- **NIH application ID:** 10910239
- **Project number:** 7P01AG051443-07
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** EBENEZER N YAMOAH
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $513,400
- **Award type:** 7
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910239

## Citation

> US National Institutes of Health, RePORTER application 10910239, Molecular and Functional Mechanisms of the aging auditory neuron (7P01AG051443-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10910239. Licensed CC0.

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