# Cell-based approach for increasing central auditory inhibition

> **NIH NIH F30** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $50,520

## Abstract

Project Summary/Abstract
Multiple lines of evidence suggest that acoustic overexposure results in cochlear damage and decreased
inhibition in auditory centers, contributing to deficits in temporal processing, tinnitus, and hyperacusis. Previous
attempts to correct this hyper-excitable state have focused on increasing GABAergic inhibitory tone
systemically, with some success in providing tinnitus relief. However, the side effect profile of these drugs
impose constraints on the dose, duration, and safety of use. A more precise treatment that locally increases
inhibition in auditory nuclei could potentially treat the underlying pathology while minimizing off-target side
effects. The inferior colliculus (IC), a major subcortical integration center of the central auditory pathway, is a
particularly apt target to explore the effects of local increases in inhibition, as it plays an important role in
mediating some acoustic behaviors (such as gap detection and pre-pulse inhibition) and demonstrates hyper-
excitable response properties following acoustic overexposure. A potential approach to increase inhibition
locally in the IC is through transplantation of cells from the medial ganglionic eminence (MGE), the birthplace
of eventual cortical inhibitory interneurons. While naturally destined for the cerebral cortex, transplanted MGE
cells have been shown to survive, integrate, and increase the number of inhibitory events in non-cortical
circuits, such as the spinal cord. As a first step toward understanding the potential role local increases in
inhibition may have in mitigating the effects of acoustic exposure, I propose to test the hypothesis that
transplanted MGE cells will functionally integrate into IC circuits in adult CBA/CaJ mice, mitigating the reduced
inhibition seen in noise exposed subjects. Three specific aims are proposed: 1) Characterize the migration and
differentiation of MGE cells transplanted into the IC of naïve and noise exposed mice. 2) Determine how
transplantation of MGE cells affects auditory behavior in adult CBA/CaJ mice. 3) Determine the effects of MGE
cell transplantation on spontaneous and sound-evoked responses of IC neurons in vivo. These experiments
represent a novel application of MGE cell transplantation and will improve our understanding of the
pathological inhibition that might underlie the formation and persistence of auditory pathologies such as tinnitus
and hyperacusis, and in the long run may lead to the development of novel treatment strategies.

## Key facts

- **NIH application ID:** 9933775
- **Project number:** 5F30DC018185-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Maryanna Owoc
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933775

## Citation

> US National Institutes of Health, RePORTER application 9933775, Cell-based approach for increasing central auditory inhibition (5F30DC018185-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9933775. Licensed CC0.

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