Tinnitus, the perception of a sound without an external source, is a complex perceptual phenomenon affecting the quality of life in 17% of the adult population in the United States. Despite its ubiquity and morbidity, the pathophysiology of tinnitus is poorly understood, and there is no universal medically recognized treatment. One of the most common causes of tinnitus is exposure to loud sounds. In humans and laboratory animals sound exposure typically leads to hearing loss, but only occasionally to tinnitus. Little i known about such resistance to sound exposure. My ultimate goal is to determine the mechanisms responsible for tinnitus resistance in tinnitus animal models to develop effective tinnitus protection in humans. The first step in identifying the mechanism(s) responsible for tinnitus resistance would be to discover a neural correlate that is differentially expressed in tinnitus positive and tinnitus negative animals. Previous research has identified several neural correlates that have tested positive for tinnitus. Abnormally high spontaneous activity has frequently been linked to tinnitus. However, while some studies demonstrate that hyperactivity positively correlates with behavioral evidence of tinnitus, others show that when all animals develop hyperactivity to sound exposure, not all exposed animals show evidence of tinnitus. This project will determine whether hyperactivity or its particular features can be used as a biomarker to separate general hearing loss from tinnitus. I will use a tinnitus mouse model that has been developed in our laboratory. Three groups of mice will be studied: (1) sound exposed mice that develop behavioral signs of tinnitus, (2) exposed mice that do not develop tinnitus, and (3) unexposed mice.
Aim 1 will determine whether hyperactivity is linked to tinnitus or/and to hearing loss. Hyperactivity in neurons of the auditory brain stem, midbrain and cortex will be assessed by measuring their spontaneous and sound-evoked firing rates during extracellular recording. Comparison of firing activity and the relative number of hyperactive neurons between these three groups of mice will test whether our hypothesis is correct.
Aim 2 will determine the cellular mechanism underlying hyperactivity in auditory neurons. Intracellular recordings will be completed on hyperactive neurons in the three groups of animals. I will measure and compare their resting membrane potentials, input resistances, spike thresholds, and firing properties. The results of this research project may differentiate tinnitus from hearing loss based on particular characteristics of hyperactivity. The proposed study will help me to master skills in two important electrophysiological techniques.
Aim 1 will provide training for single unit extracellular recordin from neurons of the major auditory centers in awake animals.
Aim 2 will allow me to acquire expertise with intracellular recording techniques using sharp glass microelectrodes. My current expertise in a behavioral tinnitus model combined with this training in electrophysiology will help me to become a capable auditory scientist.

Public Health Relevance

The pathophysiology of tinnitus, the perception of a sound without an external source, is poorly understood, and there is no universal medically recognized treatment. One of the most common causes of tinnitus is exposure to intense sounds, which often leads to hearing loss, but only occasionally to tinnitus. The goal of this proposal is to determine the neural correlate that is linked to tinnitus resistance in a tinnitus animal model.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZDC1)
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Sklare, Dan
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Northeast Ohio Medical University
Anatomy/Cell Biology
Schools of Medicine
United States
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Galazyuk, A V; Voytenko, S V; Longenecker, R J (2017) Long-Lasting forward Suppression of Spontaneous Firing in Auditory Neurons: Implication to the Residual Inhibition of Tinnitus. J Assoc Res Otolaryngol 18:343-353
Longenecker, R J; Alghamdi, F; Rosen, M J et al. (2016) Prepulse inhibition of the acoustic startle reflex vs. auditory brainstem response for hearing assessment. Hear Res 339:80-93
Longenecker, Ryan J; Galazyuk, Alexander V (2016) Variable Effects of Acoustic Trauma on Behavioral and Neural Correlates of Tinnitus In Individual Animals. Front Behav Neurosci 10:207
Grimsley, Calum A; Longenecker, Ryan J; Rosen, Merri J et al. (2015) An improved approach to separating startle data from noise. J Neurosci Methods 253:206-17