# Molecular Mechanisms of Tonotopy Development in the Brain Stem

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $326,421

## Abstract

ABSRACT
Normal nervous system maturation is dependent on neurotrophin signaling. Neurotrophins are proteins, and
along with their signaling receptor pathways, help regulate the development, maintenance and function of
vertebrate nervous systems, making it a dynamic factor that promotes biologically relevant tasks. Irregular
neurotrophin signaling results in pathophysiological conditions throughout the peripheral and central nervous
system. In the auditory periphery for example, this includes atypical arrangement of innervation patterns along
the frequency gradient (i.e., tonotopic axis) of the inner ear and hearing loss. Beyond the auditory periphery of
all vertebrates, however, the establishment of functional specialization in the central auditory pathway via
neurotrophin signaling are lacking. Understanding gradients of neurotrophin signaling is a significant and timely
problem in developmental neurobiology in general, and the avian auditory pathway proves to be a particularly
advantageous model system for experimentally examining it. A better understanding of normal auditory circuit
assembly – along with the unique functional properties of brainstem neurons – will provide a significant
foundation for developing stem cell-based therapies for auditory-related disorders. Stem cell-derived auditory
neurons will only prove useful, therapeutically, if they are able to re-create specialized functional properties that
are characteristic of normal auditory circuit maturation. A careful characterization of neurotrophin signaling, the
underlying molecular mechanism by which they operate, the role it plays in establishing normal auditory
properties and the functional consequence of altering this biological process is necessary and appropriate. The
research proposed here aims at addressing these issues by providing a comprehensive understanding of
developmental properties associated with neurotrophin signaling and its role in establishing normal functional
phenotypes along the tonotopic axis in the cochlear nucleus: a brainstem structure essential for the temporal
processing of sound.

## Key facts

- **NIH application ID:** 10424508
- **Project number:** 5R01DC017167-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jason Tait Sanchez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $326,421
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424508

## Citation

> US National Institutes of Health, RePORTER application 10424508, Molecular Mechanisms of Tonotopy Development in the Brain Stem (5R01DC017167-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10424508. Licensed CC0.

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