# Development of Neuronal Circuits In The Auditory Systems

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $531,107

## Abstract

Project Summary
Accurate and efficient auditory perception relies on precisely organized and functionally specialized neuronal
connections and synaptic circuits. The long-term goal of this research program is to elucidate the synaptic and
cellular mechanisms whereby auditory circuits in the developing brain achieve their precise functional and
structural organization. We investigate these mechanisms in the sound localization pathway from the medial
nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO). The MNTB-LSO pathway is a well-
characterized, inhibitory, glycinergic pathway with a precise tonotopic organization. During development, the
MNTB-LSO pathway undergoes a remarkable degree of reorganization, which significantly increases the
precision of its tonotopic organization. This refinement occurs to a large degree before hearing onset and
during the past funding period we have provided evidence that the precise temporal pattern of spontaneous
activity before hearing onset plays a crucial role in this reorganization. This proposal seeks to investigate the
synaptic mechanism whereby patterned activity exerts its effect on developing MNTB-LSO synapses to
regulate tonotopic refinement. To approach this we will 1) characterized the mechanism underlying activity-
dependent, patterned-sensitive long-term potentiation at inhibitory MNTB-LSO synapses before hearing onset,
2) elucidate the developmental role of GABA co-release from developing glycinergic MNTB-LSO synapses,
and 3) characterize the effects of activity-dependent zinc release from developing MNTB-LSO synapses on
synaptic transmission and reveal its role in circuit reorganization. To achieve these goals we will apply a broad
repertoire of electrophysiological, imaging, and anatomical techniques to brain slices obtained from normal and
genetically modified mice. Results from the proposed experiments will provide novel insight into basic
mechanisms governing the formation of precisely organized auditory brain circuits. Information about these
mechanisms is important to understand the biological causes that underlie developmental auditory processing
deficits in humans, including central auditory processing disorder and developmental dyslexia, which are
associated with abnormal auditory processing on the brainstem level.

## Key facts

- **NIH application ID:** 9944492
- **Project number:** 5R01DC004199-22
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Karl Kandler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $531,107
- **Award type:** 5
- **Project period:** 1999-08-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944492

## Citation

> US National Institutes of Health, RePORTER application 9944492, Development of Neuronal Circuits In The Auditory Systems (5R01DC004199-22). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9944492. Licensed CC0.

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