Chronic tinnitus is a phantom auditory sensation experienced by up to 15% of the population. Between 2 and 10% of the tinnitus population typically experience a continuous high frequency ringing or hiss sufficiently loud to impact severely on their quality of life (Cooper, 1994). Tinnitus has been found to increase with aging. Thus, the incidence of tinnitus is likely to increase due to increased longevity and recreational noise exposure. Much of the present thinking regarding the generation of tinnitus revolves around the appearance of spontaneous activity and neural hyperactivity in certain central auditory structures. A working hypothesis which parallels findings in other sensory systems suggests that partial deafferentation leads to central changes, generally involving altered inhibitory neurotransmission. Partial peripheral auditory deafferentation may produce tinnitus, coincident with a selective loss of inhibitory glycinergic function in the dorsal cochlear nucleus (DCN). Proposed studies will examine the functional and molecular neurochemical impact of aging in rats with behavioral evidence of tinnitus. Preliminary results find age and noise-exposure related changes in glycine receptor and neurotrophic factor neurochemistry in DCN of rats with behavioral evidence of tinnitus. Proposed studies will compare functional and molecular neurochemical changes between young and aged controls, and young and aged sound-exposed rats with behavioral evidence of tinnitus. Specifically: 1) quantitative measures of message and protein will be used to examine changes in the subunit make up of the glycine receptor, the scaffolding protein, gephyrin, and the protective neurotrophin BDNF;2) recordings from DCN fusiform cells will parallel behavioral studies/gap detection and examine inhibitory response properties and glycine receptor sensitivity and 3) quantitative receptor binding will be used to examine changes in glycine and neurotrophin receptor pharmacology. Findings from these studies will provide new information regarding tinnitus-related changes in glycine neurotransmission and possible neurotrophin protection in an animal model of tinnitus. Understanding the impact of aging on tinnitus-related changes in neurochemistry related to glycine and the BDNF receptor (TrkB) function might help define unique targets for the development and testing of novel selective drugs for the treatment of tinnitus.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
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Auditory System Study Section (AUD)
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Miller, Roger
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Southern Illinois University School of Medicine
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United States
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Cai, Rui; Kalappa, Bopanna I; Brozoski, Thomas J et al. (2014) Is GABA neurotransmission enhanced in auditory thalamus relative to inferior colliculus? J Neurophysiol 111:229-38
Henry, James A; Roberts, Larry E; Caspary, Donald M et al. (2014) Underlying mechanisms of tinnitus: review and clinical implications. J Am Acad Audiol 25:5-22; quiz 126
Richardson, Ben D; Brozoski, Thomas J; Ling, Lynne L et al. (2012) Targeting inhibitory neurotransmission in tinnitus. Brain Res 1485:77-87
Llano, Daniel A; Turner, Jeremy; Caspary, Donald M (2012) Diminished cortical inhibition in an aging mouse model of chronic tinnitus. J Neurosci 32:16141-8
Richardson, Ben D; Ling, Lynne L; Uteshev, Victor V et al. (2011) Extrasynaptic GABA(A) receptors and tonic inhibition in rat auditory thalamus. PLoS One 6:e16508
Wang, H; Brozoski, T J; Ling, L et al. (2011) Impact of sound exposure and aging on brain-derived neurotrophic factor and tyrosine kinase B receptors levels in dorsal cochlear nucleus 80 days following sound exposure. Neuroscience 172:453-9
Wang, Hongning; Brozoski, Thomas J; Caspary, Donald M (2011) Inhibitory neurotransmission in animal models of tinnitus: maladaptive plasticity. Hear Res 279:111-7
Hughes, Larry F; Turner, Jeremy G; Parrish, Jennifer L et al. (2010) Processing of broadband stimuli across A1 layers in young and aged rats. Hear Res 264:79-85
Roberts, Larry E; Eggermont, Jos J; Caspary, Donald M et al. (2010) Ringing ears: the neuroscience of tinnitus. J Neurosci 30:14972-9
Wang, H; Brozoski, T J; Turner, J G et al. (2009) Plasticity at glycinergic synapses in dorsal cochlear nucleus of rats with behavioral evidence of tinnitus. Neuroscience 164:747-59

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