# Neuronal control of cochlear stress responses

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2024 · $614,866

## Abstract

Project Summary
Animals, including humans, navigate through a noisy environment that can damage the ear and elicit whole body
changes in physiology and emotional state. The response to stressors such as noise is important for survival,
for instance by altering gain for improved detection of salient stimuli. However, excessive noise has dire
consequences, such as death of hair cells or neurons and their synapses. It is therefore essential to have a
balanced response to stress that is appropriate for the internal state of the animal. The goal of this project is to
study how neurons outside of the cochlea work together to protect both the cochlea and the animal from
environmental stressors. We hypothesize that stress recruits two parallel sets of efferent inputs to the cochlea:
the lateral olivocochlear neurons (LOCs) and the inner ear sympathetic neurons (IESNs). LOC axons project
from the brainstem to the organ of Corti, where they terminate on a variety of SGN subtypes across many
frequencies. IESNs housed in the stellate ganglion innervate the cochlear vasculature and regulate cochlear
blood flow, consistent with the sympathetic nervous system’s role in the fight-or-flight response. In addition,
IESNs in the superior cervical ganglion extend axons through the osseous spiral lamina, intermingling with
afferent and efferent fibers here and terminating close to the unmyelinated endings of the SGN peripheral
processes. Although a role in stress response has long been proposed, we know very little about the impact of
LOCs and IESNs on cochlear function or resilience, due in large part to the inability to manipulate either
population selectively. In preliminary studies, we characterized the molecular and anatomical properties of LOCs
and showed that they induce neuropeptides in response to noise. In addition, using genetic tools that we
established, we showed that mice lacking LOCs are more vulnerable noise-induced hearing loss than control
littermates, providing compelling evidence for a protective role in the cochlea. In parallel, we showed that IESN
axons contain pre-synaptic puncta that are apposed to afferent and efferent fibers, as well as cochlear
macrophages. Based on these observations and the known importance of neuropeptides for neuroimmune
responses in other systems, we propose that stressful stimuli activate LOCs and IESNs, which cooperate to alter
both auditory circuit activity, via their interactions with each other and the SGNs, and the immune response, with
long-lasting effects on cochlear function. To test this idea, we will use mouse genetics, viral tracing methods,
slice electrophysiology, modern in vivo recording approaches, single cell RNA-sequencing, and in vivo assays
to characterize LOC responses to noise and other stressors, to map the molecular and anatomical properties of
IESNs, and to investigate how LOCs and IESNs impact the immune system and hence cochlear health.

## Key facts

- **NIH application ID:** 10855234
- **Project number:** 1R01DC021692-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Lisa Goodrich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $614,866
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10855234

## Citation

> US National Institutes of Health, RePORTER application 10855234, Neuronal control of cochlear stress responses (1R01DC021692-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10855234. Licensed CC0.

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