# Corticostriatal Contributions to Auditory Perceptual Hypersensitivity

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2021 · $33,743

## Abstract

Project Summary/Abstract
Across sensory systems, a deprivation of peripheral input is associated with a compensatory increase in neural
excitability at the level of sensory cortex. Commonly, this compensatory process overshoots the mark, resulting
in hyperactivity along with perceptual hypersensitivity to sensory stimuli. Such observations have a long history
in the auditory system: noise-induced damage to the cochlea is associated with a paradoxical cortical
hyperactivity and perceptual abnormalities such as hyperacusis, an auditory disorder characterized by an
increase in perceived loudness to moderately intense sounds. Although it is believed that cortical hyperactivity
is a driving force behind perceptual hypersensitivity, a definitive link is yet unclear. This mentored training
project will combine chronic behavioral, two-photon imaging, and optogenetics techniques in mice to
understand the neural changes underlying the emergence of a behavioral hypersensitivity phenotype following
a high frequency noise-induced hearing loss. Studies pursuant to Aim 1 will develop a two-alternative forced
choice task that assesses loudness perception in head-fixed mice. Such a behavior provides two major
advances: i) direct evaluation of perceptual hypersensitivity after noise exposure, and ii) the ability to do
chronic imaging in behaving mice. Studies in Aim 2 will use chronic two-photon calcium imaging of auditory
corticostriatal neurons, a defined cell type directly relevant to auditory-guided behavior. Imaging will take place
in both passive and task-engaged conditions both to allow full characterization of frequency and intensity
response changes across the tonotopic map and to enable direct comparison of neural activity changes with
perceptual decision-making. Aim 3 will test the hypothesis that inducing auditory corticostriatal hyperexcitability
in unexposed control mice with healthy cochleae is sufficient to increase the probability of perceptually
categorizing moderately intense sounds as loud. Corticostriatal neurons will be shifted in and out of
hyperactive states using stabilized step function opsins to temporarily induce stable and reversible planes of
hyperexcitability in normal, behaving mice. Altogether, this project will overcome previous technical limitations
to gain a more complete understanding of the neural circuit pathology underlying auditory perceptual
hypersensitivity. Beyond peripheral injury, sensory hypersensitivity is associated with other conditions such as
aging and neurodevelopmental disorders including autism. Thus, insight from this project into the neural
signatures of hyperactivity and behavioral hypersensitivity will prove valuable broadly for hearing impairment,
other sensory disorders, and related neurological conditions.

## Key facts

- **NIH application ID:** 10163669
- **Project number:** 5F31DC018974-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Matthew McGill
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,743
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163669

## Citation

> US National Institutes of Health, RePORTER application 10163669, Corticostriatal Contributions to Auditory Perceptual Hypersensitivity (5F31DC018974-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10163669. Licensed CC0.

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