# Age-related GABAergic loss in the central auditory circuits

> **NIH NIH R01** · NORTHEAST OHIO MEDICAL UNIVERSITY · 2021 · $331,500

## Abstract

Project Summary
Our long-term goal is to understand the relationship between peripheral and central changes in the auditory
system during age-related hearing loss (ARHL). GABA, an inhibitory neurotransmitter critical for precise
temporal processing, is downregulated in the central auditory system during aging. This loss of GABA has
been best documented in the inferior colliculus (IC), an auditory nucleus that gives rise to ascending circuits
that carry temporally precise signals to the auditory cortex for perception and descending circuits that play a
pivotal role in the temporal processing of interpreting speech from noise. Recent studies hypothesize that the
downregulation of GABA is a homeostatic response to “re-up” the gain in central neurons as the cochlear input
is diminished. However, our understanding of GABAergic function in the aging IC is inadequate due to the lack
of information about the relationship of GABA loss to increasing hearing deficits, about which specific IC
circuits lose GABA, and how those circuits respond during aging.
Our central hypothesis is that age-related GABAergic downregulation in the IC occurs prior to the onset of
auditory processing deficits and in two stages: an initial loss of GABA prior to age-related auditory processing
deficits that is associated with descending IC circuits, and a subsequent loss associated with the ascending IC
circuits. The objective of this proposal is to determine where in the IC age-related changes of GABA occur and
if so, do these changes occur before the onset of auditory processing deficits. The experiments will combine
data from gap detection using the prepulse inhibition of the acoustic startle, envelope following responses,
auditory brainstem responses, immunochemistry and immunoelectron microscopy-intersectional viral tracing to
determine age-related GABAergic changes in the IC that occur before hearing deficits. Examining the
relationship between the loss of GABAergic cells, boutons and synapses in the aging IC before the onset of
hearing deficits is the focus of Aim 1. Aim 2 will determine if specific IC circuits lose GABAergic input with age
and if so, when those losses occur relative to each other. Aim 3 will identify when inhibitory and excitatory IC
circuits change their GABAA receptor subunit composition to compensate for the declining levels of GABAergic
input during ARHL.
Data generated from these three Aims will move the field forward by establishing precise points in time when
age-related changes in specific circuits of the central auditory system occur in relation to hearing loss. The
results will provide essential information for designing and interpreting future experiments with viral tracing,
physiology and behavior to investigate GABAergic function in the aging auditory system.

## Key facts

- **NIH application ID:** 10221666
- **Project number:** 5R01DC017708-02
- **Recipient organization:** NORTHEAST OHIO MEDICAL UNIVERSITY
- **Principal Investigator:** Jeffrey Garrett Mellott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $331,500
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221666

## Citation

> US National Institutes of Health, RePORTER application 10221666, Age-related GABAergic loss in the central auditory circuits (5R01DC017708-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10221666. Licensed CC0.

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