The overall aim is to examine the mechanisms underlying pathophysiologic changes in neural coding in the auditory nerves of animals aged in quiet. Over the past 10 years they have successfully developed the Mongolian gerbil as a model of human presbyacusis. In this proposal we focus on one cochlear potential in the gerbil model known to be affected by age: the endocochlear potential (EP) produced by the lateral wall system. We examine the relationship between the EP and neural coding in young and aged animals. Specific focus is on the effects of EP on the processing of temporal information in auditory nerve fibers, an aspect not yet addressed in the literature in the normal cochlea, much less in the presbyacusic cochlea. There are three specific aims.
Specific aim 1 examines neural coding of timing information in the auditory nerves of young and quite-aged gerbils. Experiments include single fiber studies and population studies using the compound action potential (CAP). The hypothesis to be tested is that temporal coding in quiet-aged animals becomes deficient with age.
Specific Aim 2 acutely manipulates the EP in old and young gerbils to test the hypothesis that the EP plays a fundamental role in the coding of temporal information in auditory-nerve activity.
Specific Aim 3 examines neural coding under conditions of a chronically low EP in young gerbils. The lowered EP will be maintained by infusing furosemide into the cochlea with an implanted cannula and osmotic pump over periods ranging from weeks to months. Previous work supports the hypothesis that ;the quiet-aged gerbil cochlea can be modeled as an intact hair cell system operating under conditions of a low EP. The last aim will establish a model of presbyacusic cochlea in a young animal, thereby greatly enhancing the efficiency of studies of presbyacusis in animal models.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG014748-04
Application #
6168961
Study Section
Hearing Research Study Section (HAR)
Program Officer
Finkelstein, Judith A
Project Start
1997-09-01
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
4
Fiscal Year
2000
Total Cost
$162,462
Indirect Cost
Name
Medical University of South Carolina
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Lang, Hainan; Jyothi, Vinu; Smythe, Nancy M et al. (2010) Chronic reduction of endocochlear potential reduces auditory nerve activity: further confirmation of an animal model of metabolic presbyacusis. J Assoc Res Otolaryngol 11:419-34
Lang, Hainan; Schulte, Bradley A; Goddard, John C et al. (2008) Transplantation of mouse embryonic stem cells into the cochlea of an auditory-neuropathy animal model: effects of timing after injury. J Assoc Res Otolaryngol 9:225-40
Lang, Hainan; Schulte, Bradley A; Zhou, Daohong et al. (2006) Nuclear factor kappaB deficiency is associated with auditory nerve degeneration and increased noise-induced hearing loss. J Neurosci 26:3541-50
Moody, Marcus W; Lang, Hainan; Spiess, Adam C et al. (2006) Topical application of mitomycin C to the middle ear is ototoxic in the gerbil. Otol Neurotol 27:1186-92
Lang, H; Schulte, B A; Schmiedt, R A (2005) Ouabain induces apoptotic cell death in type I spiral ganglion neurons, but not type II neurons. J Assoc Res Otolaryngol 6:63-74
Mills, David M; Schmiedt, Richard A (2004) Metabolic presbycusis: differential changes in auditory brainstem and otoacoustic emission responses with chronic furosemide application in the gerbil. J Assoc Res Otolaryngol 5:1-10
Wang, Yong; Meng, Aimin; Lang, Hainan et al. (2004) Activation of nuclear factor kappaB In vivo selectively protects the murine small intestine against ionizing radiation-induced damage. Cancer Res 64:6240-6
Lang, H; Schulte, B A; Schmiedt, R A (2003) Effects of chronic furosemide treatment and age on cell division in the adult gerbil inner ear. J Assoc Res Otolaryngol 4:164-75
Schmiedt, Richard A; Lang, Hainan; Okamura, Hiro-oki et al. (2002) Effects of furosemide applied chronically to the round window: a model of metabolic presbyacusis. J Neurosci 22:9643-50
Spector, A A; Ameen, M; Schmiedt, R A (2002) Modeling 3-D deformation of outer hair cells and their production of the active force in the cochlea. Biomech Model Mechanobiol 1:123-35

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