# Uncovering the Functional Effects of Neurotrophins in the Auditory Brainstem

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2023 · $42,907

## Abstract

PROJECT SUMMARY/ABSTRACT
Neurotrophins are secreted signaling proteins that promote the growth and organization of developing neurons.
Gradients of expression of the neurotrophin and its associated tyrosine receptor kinase (Trk) allow for
spatiotemporally regulated signaling that promotes synapse strengthening and neuronal maturation. For
example, Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is secreted within the developing avian
auditory brainstem. Its receptor, tryrosine receptor kinase B (TrkB), is highly expressed early in embryonic
development and systematically decreases to negligible amount by the time the embryo hatches. While
neurotrophin signaling is essential to induce cellular and synaptic maturation in other neural tissues, its direct
effects on the development and functionality of the central auditory system remains unknown.
Temporal precision is essential for auditory brainstem neurons to accurately encode the complexities of sound.
Therefore, the objective of this research proposal is to determine how neurotrophin signaling affects intrinsic ion
channel properties responsible for establishing functional phenotypes for the roles they subserve: binaural
hearing and sound localization. Specifically, I will investigate the role of the BDNF/TrkB signaling pathway on
defining the intrinsic phenotype of auditory brainstem neurons. I will additionally test the importance of
neurotrophin regulation on the development of mature and robust auditory brainstem signaling in response to
sound.
The central hypothesis of this research proposal is that altered neurotrophin signaling in the auditory brainstem
will decrease the ability for auditory brainstem neurons to transmit information in a temporally reliable manner.
In Aim 1 I will use patch clamp electrophysiology to determine the effects of aberrant neurotrophin signaling on
the intrinsic properties of auditory brainstem neurons. In Aim 2 I will assess the functional ramifications of
irregular neurotrophin signaling by measuring electrical field potentials from auditory brainstem structures.
Collectively, this research will elucidate the importance of neurotrophin signaling at the cellular and systems level
within the auditory brainstem, providing possible candidates for developmental signals that may be dysregulated
in early central auditory-related disorders.

## Key facts

- **NIH application ID:** 10823506
- **Project number:** 1F31DC021366-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Kristine McLellan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $42,907
- **Award type:** 1
- **Project period:** 2024-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823506

## Citation

> US National Institutes of Health, RePORTER application 10823506, Uncovering the Functional Effects of Neurotrophins in the Auditory Brainstem (1F31DC021366-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10823506. Licensed CC0.

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