# Type II Afferents and Cochlear Damage

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $623,946

## Abstract

Project Summary
Auditory stimuli travel from the cochlea to the brainstem through type I and type II cochlear afferents. While
type I afferents convey information about the frequency, intensity, and timing of sounds, the role of type II
afferents remains unresolved. Limited recordings of type II afferents from the cochlear apex in pre-hearing rats
reveal that they can be activated by widespread outer hair cell (OHC) stimulation and by ATP released by
acute tissue damage. Secondly, synaptic activity in type II fibers has been shown to be glutamatergic but input
from multiple OHCs is required to initiate action potential firing. A recent study suggests that type II afferents
respond to non-damaging sound, via their glutamatergic pathway. Additionally, type II fibers exhibit properties
similar to pain fibers, for example the expression of modulatory peptidergic and cannabinoid signaling
pathways. Finally, type II fibers express receptor genes to inflammatory modulators, some of which are
upregulated after noise exposure. These combined data suggest that type II afferents may sense non-
damaging and damaging sound levels, and that multiple parallel pathways may contribute to the type II fiber
response to different degrees, depending on history of sound exposure. To explore this hypothesis, we have
developed Ca2+-imaging techniques that reveal type II fiber activity throughout the cochlear coil, from apex to
base, of adult mice. Secondly, we propose to use loose patch recordings of type II afferent fibers to monitor
firing rates in response to optogenetic stimulation of OHCs. Both approaches are utilized to determine the
impact of non- damaging and damaging sound exposure on the activity of type II cochlear afferents. The goal
of this proposal is to understand the contribution of multiple pathways (purinergic, glutamatergic,
neuromodulatory and inflammatory) to these conditions. Our recent experiments show sensitization in the type
II afferent response following noise exposure. Such sensitization might be reflective of a `gain-of-function
pathology' like hyperacusis/noxacusis. The proposed comprehensive approach here aims to identify
pharmacotherapeutic targets for such gain of function pathologies that can follow noise exposure and noise-
induced hearing loss.

## Key facts

- **NIH application ID:** 10867505
- **Project number:** 5R01DC016559-08
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ELISABETH GLOWATZKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $623,946
- **Award type:** 5
- **Project period:** 2017-06-16 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867505

## Citation

> US National Institutes of Health, RePORTER application 10867505, Type II Afferents and Cochlear Damage (5R01DC016559-08). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10867505. Licensed CC0.

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