Tinnitus affects up to 1/3 of the U.S. population with symptoms severe and disabling enough in about 10% of the population to have a significant impact on quality of life. Despite the prevalence of tinnitus, the pathophysiology of tinnitus remains largely unknown. The current proposal seeks to develop a rapid behavioral assessment of tinnitus in laboratory rats. We hypothesized that if a background acoustic signal is qualitatively similar to an animal's tinnitus, detection of a silent gap in this background would be impaired. Recently published initial studies support this hypothesis. Rats with independent psychophysical evidence of tinnitus at 10 kHz (n=14) exhibited significantly worse gap detection than controls (n=13) when the gap was embedded in a background similar to their putative tinnitus. No differences between tinnitus and control animals were found with 16 kHz or broadband noise backgrounds, helping rule out the possibility of hearing loss or general performance deficits. Thus, initial results using a startle gap detection procedure found that rats with tinnitus were deficient in detecting a silent gap in an acoustic background similar to their tinnitus. Proposed studies will attempt to refine and further validate this method as a tinnitus screen for rats. Specifically, these studies will systematically vary the spectral characteristics of the background signal (Aim#1), the intensity of the background signal (Aim #2) and the duration and rise/fall characteristics of the gap (Aim #3).
Aim #4 will assess the usefulness of this procedure as a method to screen for effective antitinnitus agents. Gabapentin, a drug shown to have the potential to attenuate tinnitus in animals and humans, will be tested using the gap detection method. The proposed studies are necessary steps in the development of this method and should elucidate the critical features of gap detection that are deficient in animals with tinnitus. Once established, this approach for tinnitus screening would obviate the need for food or water deprivation and prior behavioral training. Startle gap detection is a measure of reflex modulation so it places no learning, memory or motivational demands on the animal. This feature makes it useful for aging studies or drug studies where learning/memory and motivational systems might be compromised. The potential development of novel pharmacological or other manipulations to ameliorate tinnitus is enhanced by the establishment of a simple, 30-40 min screening test for tinnitus in an animal model. ? ? ?
| Turner, Jeremy G; Parrish, Jennifer L; Zuiderveld, Loren et al. (2013) Acoustic experience alters the aged auditory system. Ear Hear 34:151-9 |
| Turner, Jeremy; Larsen, Deb; Hughes, Larry et al. (2012) Time course of tinnitus development following noise exposure in mice. J Neurosci Res 90:1480-8 |
| Ding, Ming; Arnold, Jennifer; Turner, Jeremy et al. (2010) Lack of association of a spontaneous mutation of the Chrm2 gene with behavioral and physiologic phenotypic differences in inbred mice. Comp Med 60:272-81 |
| Turner, Jeremy G; Parrish, Jennifer (2008) Gap detection methods for assessing salicylate-induced tinnitus and hyperacusis in rats. Am J Audiol 17:S185-92 |
| Turner, Jeremy G (2007) Behavioral measures of tinnitus in laboratory animals. Prog Brain Res 166:147-56 |
| Turner, Jeremy G; Bauer, Carol A; Rybak, Leonard P (2007) Noise in animal facilities: why it matters. J Am Assoc Lab Anim Sci 46:10-3 |
