# Mechanisms of Growth Factor Responsiveness in the Aging Auditory System

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2022 · $305,564

## Abstract

Primary auditory afferent neurons conduct sound-evoked action potentials (APs) through surprisingly small
diameter axons at remarkable speed and with millisecond precision. The response properties of the auditory
neuron (AN) are phased-locked for low-frequency (<5 kHz) sounds, suggesting that conduction failure is a rarity.
However, the neural mechanisms that enable swift and phase-locked conduction are poorly understood. We
hypothesize that ANs utilize non-uniform nodal, internodal, and patchy nodal ionic channel distribution to
maintain fast conduction velocity (CV). These features optimize action potential (AP) CV and prevent AP
conduction failure despite the structural limitations of the AN. We propose to test the underlying hypotheses
using various knockin and knockout mouse models and pharmacological strategies. We utilize innovations such
as optogenetics, high-resolution microscopy, and multiple electrophysiological approaches. We aim to determine
1) AN axonal ion channels' expression, colocalization, and interactions. We will employ multidisciplinary
approaches to assess the expression distribution of specific ionic channels in AN axons. 2) The functional and
physical interactions between specific ionic channels in AN neurites. The proximity of certain channels shapes
the APs of ANs for high-speed conduction. We will use proximity ligation assay (PLA), live-cell imaging, and
spatial and temporal resolution recordings to quantify the protein-protein interactions. 3) Axonal ionic channels'
ex vivo and in vivo functional roles of ion channels that shape AN AP CV will be examined. We will use patch-
clamp analyses of the kinetics, voltage dependence, and conductance in AN neurons to determine the underlying
mechanisms for the differences in response properties and CV using computational studies. Thus, we will
address the complexity of anatomic projections and signal processing and subsequent alterations of the
structural and ionic conductances that would alter AP CV. This information is a necessary step toward developing
treatments for hearing loss.

## Key facts

- **NIH application ID:** 11178141
- **Project number:** 7R01AG060504-06
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** EBENEZER N YAMOAH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $305,564
- **Award type:** 7
- **Project period:** 2018-08-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11178141

## Citation

> US National Institutes of Health, RePORTER application 11178141, Mechanisms of Growth Factor Responsiveness in the Aging Auditory System (7R01AG060504-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11178141. Licensed CC0.

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