# Alterations and mechanisms of auditory information processing in the aging auditory pathway

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2024 · $423,738

## Abstract

Abstract
Age-related hearing loss (ARHL), also referred to as presbycusis, is a complex degenerative disease
characterized by hearing impairment. The condition is a significant public health problem, affecting 40% of
individuals aged between 55 and 74. ARHL is attributed to central and peripheral auditory system degeneration.
Central ARHL refers to age-associated degeneration in the auditory portion of the central nervous system, which
affects the ability to localize the temporal and spatial origins of sounds and impairs speech understanding in
noisy environments. However, studies so far have not fully elucidated the cellular mechanisms underlying deficits
to temporal precision of sound localization and speech understanding in aging. In Aim 1, we will determine the
age-dependent structural and molecular remodeling of central auditory synapses. We hypothesize that
aging alters key structural and molecular parameters at the central synapses. As a result, the endbulb and calyx
of Held synapses exhibit decreased activity. Studies in Aim 2 will determine the age-dependent structural
and molecular remodeling of central nerve axonal fibers. We hypothesize that age-related deficits in myelin
and internode distance along the auditory nerve and calyx axonal fibers will decrease conduction velocity (CV)
and degrade synaptic activity. In addition, another most notable change in ARHL is an increase in neuronal
excitability. The degradation of input at the auditory neural axis periphery shifts the balance of excitation and
inhibition throughout the auditory hierarchy, including the cochlear nucleus (CN), superior olivary complex (SOC),
and auditory cortex (ACtx). It leads to altered neuronal excitability and auditory dysfunctions, including tinnitus
and hyperacusis. Although altered neuronal excitability (“hypo-” or “hyper”-excitability) has been found in several
brain stations in the ascending auditory hierarchy, its presence in descending systems is less understood. We
hypothesize that the mechanism of altered age-related neuronal excitability in the ACtx stems from modified CN
and SOC pre- and post-synaptic properties, as well as neuronal demyelination. In Aim 3, we will identify
structural changes in pyramidal tract (PT) projection pathways in the aging brain. We hypothesize that
aging incurs structural plasticity in PT projection neurons' downstream targets. Studies in Aim 4 will determine
sensory processing deficits in PT projection pathways in the aging brain. We hypothesize that altered
excitability in the aged auditory system systematically degrades the spectrotemporal processing of sound. The
overall goal in this project (P3) is to understand the age-dependent structural and molecular remodeling of central
auditory synapses and central nerve axonal fibers, as well as providing novel insights into how aging influences
structural plasticity throughout the auditory system and how connectivity with downstream brain areas are altered
in aging.

## Key facts

- **NIH application ID:** 10910249
- **Project number:** 7P01AG051443-07
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Maria-Eulalia Rubio-Valero
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $423,738
- **Award type:** 7
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910249

## Citation

> US National Institutes of Health, RePORTER application 10910249, Alterations and mechanisms of auditory information processing in the aging auditory pathway (7P01AG051443-07). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10910249. Licensed CC0.

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