# Cellular Mechanisms of Auditory Information Processing

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $543,091

## Abstract

Hearing loss is a pervasive problem that can result from exposure to loud sounds, to drugs for treatment
of cancer and infections, from aging, or from individual genetic factors. Noise-induce hearing loss (NIHL),
from both occupational and recreational causes, is a growing issue that is currently is thought to affect
more than 40 million Americans. Nearly 25% of adults have audiological signs consistent with causation
by NIHL. Hearing loss leads to difficulties in communication, social isolation, and possibly to changes in
cognition. Most causes of hearing loss are caused by dysfunctional changes in the cochlea and spiral
ganglion cells, which in turn provided a degraded sensory representation to the cochlear nucleus (CN)
where the axons of spiral ganglion cells, the auditory nerve fibers (ANFs), terminate. The consequences
of cochlear NIHL then propagate throughout the central auditory system, engaging pathophysiological
increases in excitability and altering synaptic function. The CN consists of networks of neurons with distinct
patterns of synaptic innervation from ANFs, and these neurons create parallel, yet intertwined, pathways
for upstream analysis. Although sensory processing in the CN has been well studied in animals with normal
cochleae, how the mechanisms and functions of CN circuits change after hearing loss, and the
consequences of those changes for sensory processing, is not as well understood. Many cellular
mechanisms have only been studied in juvenile mice during a developmental sensitive period. There is an
unmet need to understand the unique cellular mechanisms underlying NIHL that occur in adults. Here, we
propose to use controlled NIHL to perturb the ANF inputs to the CN, and then to examine specific synapses
and cellular excitability mechanisms related to sensory processing in noisy environments in the CN. First,
we will examine the hypothesis that NIHL leads to increased excitability of three specific populations of CN
neurons, two of which have not been studied, and one that has only been studied in very young animals,
in brain slices in adult mice. We will determine which specific mechanisms and ion channels are causal to
changes in excitability. Second, we will examine how the synaptic inputs to different neurons of the CN are
affected by NIHL, testing the hypotheses that NIHL induces mechanisms that amplify residual dendritic
excitatory synaptic inputs, and alter the functional organization and strength of inhibition at specific local
connections. Third, we will examine how the detection of sounds in noise is affected by NIHL in these three
populations of CN neurons, using an established acoustic paradigm, in both computational models and in
vivo. Together the results from these studies will provide insights into how the early stage processing of
sound is affected by hearing loss, and can contribute identifying approaches to optimize sensory
discrimination after hearing loss.

## Key facts

- **NIH application ID:** 10072593
- **Project number:** 1R01DC019053-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Paul B Manis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $543,091
- **Award type:** 1
- **Project period:** 2020-06-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072593

## Citation

> US National Institutes of Health, RePORTER application 10072593, Cellular Mechanisms of Auditory Information Processing (1R01DC019053-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072593. Licensed CC0.

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