# Neuronal hyperactivity: tinnitus and distress

> **NIH NIH R01** · NORTHEAST OHIO MEDICAL UNIVERSITY · 2022 · $407,747

## Abstract

Tinnitus is a phantom sound perception that affects about 17% of adults in the United States. There are
currently no FDA-approved drugs for tinnitus treatment. Both human imaging studies and animal research
suggest that tinnitus is linked to hyperactivity in central auditory neurons following cochlear insult. Tinnitus-
related hyperactivity has commonly been described as an elevated spontaneous firing and increased neural
synchrony. The goal of this study is to elucidate the cellular mechanism(s) responsible for hyperactivity and to
identify pharmacological therapy for controlling hyperactivity to relieve tinnitus symptoms. Recent research
has identified two possible mechanisms that may be responsible for tinnitus-related hyperactivity: down-
regulation of GABAergic inhibition and changes in the intrinsic properties of affected neurons. Little is known
about the relative contributions of these two mechanisms to the hyperactivity. We will address this question by
studying intrinsic properties of auditory neurons in conjunction with intracellular labeling and immunostaining
for GABAergic neurons. “Residual inhibition”, the brief suppression of tinnitus after presentation of loud
sounds, can be induced in about 80% of tinnitus patients. We discovered that the mechanism of residual
inhibition is likely explained by sound-evoked suppression of spontaneous firing in central auditory neurons,
and that metabotropic glutamate receptors (mGluRs) play a critical role in this suppression. We propose that
elevated spontaneous firing and neural synchrony are neural correlates of tinnitus and that their suppression
should bring relief from tinnitus. Our preliminary data indicate that systemic application of the group II mGluR
agonist Eglumegad reliably suppresses spontaneous firing in inferior colliculus (IC) and auditory cortex (AC)
neurons in mice for about two hours. Sound-evoked activity is negligibly affected by this drug. Similar drug
effects were observed in the amygdala, a brain structure likely to be involved in tinnitus-related distress.
Furthermore, Eglumegad applied systemically suppressed tinnitus in mice for more than one hour. Three
hypotheses will be tested. First, we hypothesize that mice show tinnitus-related hyperactivity like other animal
models. Conventional extracellular and multi-electrode array recordings will be used to assess spontaneous,
sound-evoked firing and neural synchrony in neurons of the AC, IC, and amygdala in tinnitus positive and
control mice. Second, we hypothesize that excitatory and inhibitory neurons are differentially affected by
hyperactivity. Intracellular recordings using sharp microelectrodes will be conducted in the IC of awake mice
followed by intracellular labeling with neurobiotin and then immunochemistry to distinguish GABAergic vs non-
GABAergic neurons. Third, we hypothesize that activation of group II mGluRs can reduce hyperactivity in the
AC, IC, and amygdala and also suppress tinnitus and tinnitus-related...

## Key facts

- **NIH application ID:** 10318516
- **Project number:** 5R01DC016918-04
- **Recipient organization:** NORTHEAST OHIO MEDICAL UNIVERSITY
- **Principal Investigator:** Alexander Galazyuk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $407,747
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318516

## Citation

> US National Institutes of Health, RePORTER application 10318516, Neuronal hyperactivity: tinnitus and distress (5R01DC016918-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10318516. Licensed CC0.

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