Intense noise exposure and ototoxic drugs cause hearing loss and reduce the neural output of the cochlea. Paradoxically, cochlear damage often enhances neural activity in the central auditory pathway at suprathreshold intensities. This compensatory increase in the central auditory pathway is referred to as Enhanced Central Gain. Enhanced Central Gain is believed to be responsible for hyperacusis (loudness intolerance) and tinnitus, two debilitating conditions that afflict millions of Americans. The goal of this project s to experimentally test the Central Gain model to determine if it can account for hyperacusis and tinnitus induced by ototoxic drugs or intense noise exposure. To accomplish this, we will determine if the temporal and spectral properties of noise-induced or drug-induced hyperacusis match time course and spectral features of the electrophysiological metric of increased central gain in auditory cortex (AC), medial geniculate body (MGB), lateral amygdala and inferior colliculus (IC). We will also determine if the time course of noise-induced or drug- induced tinnitus is correlated with the time course and spectral features of hyperacusis and increased central gain in the AC, MGB, LA or IC. Since hyperexcitability disorders can be controlled by drugs that regulate potassium channel permeability, we will test the hypothesis that potassium channel modulators can suppress noise- or drug-induced hyperacusis and enhanced central gain. The proposed studies are designed to increase our understanding of the neural mechanisms of hyperacusis and tinnitus and test the efficacy of novel pharmacological agents to treat these two debilitating disorders.

Public Health Relevance

Individuals with hearing loss suffer from hyperacusis (loudness intolerance) and tinnitus, conditions thought to arise from increased neural gain in the central auditory pathway. Experiments are planned to determine if the time course and spectral features of increased central gain matches the time course and spectral properties of tinnitus and hyperacusis. Potassium channel modulators, used to treat hyperexcitability disorders, will be evaluated to determine if they can suppress hyperacusis and decrease central gain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC014452-05
Application #
9824577
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Miller, Roger
Project Start
2015-12-01
Project End
2020-11-30
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Other Health Professions
Type
Schools of Arts and Sciences
DUNS #
038633251
City
Amherst
State
NY
Country
United States
Zip Code
14228
Zhang, Jianhui; Sun, Hong; Salvi, Richard et al. (2018) Paraquat initially damages cochlear support cells leading to anoikis-like hair cell death. Hear Res 364:129-141
Zhao, Deng-Ling; Sheppard, Adam; Ralli, Massimo et al. (2018) Prolonged low-level noise exposure reduces rat distortion product otoacoustic emissions above a critical level. Hear Res 370:209-216
Chen, Guang-Di (2018) Hidden cochlear impairments. J Otol 13:37-43
Sheppard, Adam M; Zhao, Deng-Ling; Salvi, Richard (2018) Isoflurane anesthesia suppresses distortion product otoacoustic emissions in rats. J Otol 13:59-64
Baizer, Joan S; Wong, Keit Men; Salvi, Richard J et al. (2018) Species Differences in the Organization of the Ventral Cochlear Nucleus. Anat Rec (Hoboken) 301:862-886
Manohar, Senthilvelan; Spoth, Jaclyn; Radziwon, Kelly et al. (2017) Noise-induced hearing loss induces loudness intolerance in a rat Active Sound Avoidance Paradigm (ASAP). Hear Res 353:197-203
Sheppard, Adam M; Chen, Guang-Di; Manohar, Senthilvelan et al. (2017) Prolonged low-level noise-induced plasticity in the peripheral and central auditory system of rats. Neuroscience 359:159-171
Jiang, Chen; Luo, Bin; Manohar, Senthilvelan et al. (2017) Plastic changes along auditory pathway during salicylate-induced ototoxicity: Hyperactivity and CF shifts. Hear Res 347:28-40
Chen, Yu-Chen; Chen, Guang-Di; Auerbach, Benjamin D et al. (2017) Tinnitus and hyperacusis: Contributions of paraflocculus, reticular formation and stress. Hear Res 349:208-222
Seigel, G M; Manohar, S; Bai, Y Y et al. (2017) An immortalized microglial cell line (Mocha) derived from rat cochlea. Mol Cell Neurosci 85:202-210

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