# Fast Inhibition in the Sound Localization Pathway

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $379,573

## Abstract

Project Summary:
Sound localization – determining where in space a sound originates – is a cardinal task of the auditory system.
While much progress has been made in uncovering the fundamental neural processes that mediate sound
localization, there still remain significant gaps that limit our understanding of the underlying circuit. Here we
focus on the role played by one key component of the sound localization circuit, the medial nucleus of the
trapezoid body (MNTB), and its inhibitory output.
The overarching hypothesis of this proposal is that fast MNTB inhibition is essential for the neural
computation of ITDs and IIDs at the two sound main localization nuclei, the medial and lateral superior olive
(MSO and LSO, respectively). In addition, we propose that MNTB inhibition will have a sufficiently large effect
on the generation of wave III of auditory brainstem responses (ABRs), such that suppression of MNTB will
alter this wave. ABRs are a method that non-invasively measure in-vivo the activity of brain stem neurons, and
we focus on wave III because in rodents this wave is commonly associated with activity of neurons in the sound
localization nuclei.
To test the hypothesis, we will optogenetically manipulate MNTB and record MSO activity to discriminate
between several competing models of sound localization by MSO neurons (Aim 1). Then we will optogenetically
manipulate MNTB and record low-frequency LSO activity to study a population of low-frequency LSO neurons
(Aim 2). Finally, we will optogenetically suppress MNTB and record responses and effects on the ABR (Aim 3).
This manipulation mimics similar ABR alterations in common hearing conditions affecting binaural hearing.
Overall, the aims are designed to enhance our understanding of sound localization mechanisms in the auditory
brainstem, the brain area that performs the first separation of multiple sounds from each other based on their
spatial location. There are a number of medical conditions in which alterations in this pathway lead to a
patient's decreased ability to localize sound and function in a noisy environment. A better understanding of the
neural mechanisms in this circuit in the healthy auditory system will help design treatments for these
conditions in the future.

## Key facts

- **NIH application ID:** 9876685
- **Project number:** 1R01DC018401-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Achim Klug
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $379,573
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876685

## Citation

> US National Institutes of Health, RePORTER application 9876685, Fast Inhibition in the Sound Localization Pathway (1R01DC018401-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9876685. Licensed CC0.

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