The study describes a novel method for tinnitus screening in rats by use of gap detection reflex procedures. The authors hypothesized that if a background acoustic signal was qualitatively similar to the rat's tinnitus, poorer detection of a silent gap in the background would be expected. Rats with prior 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 tinnitus. No differences between tinnitus and control rats were found with 16 kHz or broadband noise backgrounds, which helped to rule out explanations related to hearing loss or general performance deficits. The results suggest that gap detection reflex procedures might be effective for rapid tinnitus screening in rats.

Fifteen to 35% of the United States population experiences tinnitus, a subjective "ringing in the ears". Up to 10 percent of those afflicted report severe and disabling symptoms. Tinnitus was induced in rats using unilateral, one-hour, 17 kHz-centered octave-band noise (116 dB SPL) and assessed using a gap-startle method. The dorsal cochlear nucleus (DCN) is thought to undergo plastic changes suggestive of altered inhibitory function during tinnitus development. Exposed rats showed near preexposure ABR thresholds for clicks and all tested frequencies 16 weeks post-exposure. Soundexposed rats showed significantly worse gap detection at 24 and 32 kHz 16 weeks following sound exposure, suggesting the development of chronic, high frequency tinnitus.Message and protein levels of α 1-3 , and β glycine receptor subunits (GlyRs), and the anchoring protein, gephyrin, were measured in DCN fusiform cells 4 months following sound exposure. Rats with evidence of tinnitus showed significant GlyR α 1 protein decreases in the middle and high frequency regions of the DCN while α 1 message levels were paradoxically increased. Gephyrin levels showed significant tinnitus-related increases in sound-exposed rats suggesting intracellular receptor trafficking changes following sound exposure. Consistent with decreased α 1 subunit protein levels, strychnine binding studies showed significant tinnitus-related decreases in the number of GlyR binding sites, supporting tinnitus-related changes in the number and/or composition of GlyRs.Collectively, these findings suggest the development of tinnitus is likely associated with functional GlyR changes in DCN fusiform cells consistent with previously described behavioral and neurophysiologic changes. Tinnitus related GlyR changes could provide a unique receptor target for tinnitus pharmacotherapy or blockade of tinnitus initiation. Keywordshearing loss; sound exposure; fusiform cell; auditory; glycine receptor; gephyrin Correspondence to: Dr. Donald M. Caspary, Phone: 217-545-2195, Fax: 217-545-0145, dcaspary@siumed.edu. Section Editor: Sensory Systems: Dr. Richard Weinberg, University of North Carolina, Department of Cell Biology and Anatomy, CB 7090, Chapel Hill, NC 27599, USA Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 December 1. Published in final edited form as:Neuroscience. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptTinnitus is a common audiologic complaint characterized by auditory perception without an external phys...

Presbycusis can be considered a slow age-related peripheral and central deterioration of auditory function which manifests itself as deficits in speech comprehension, especially in noisy environments. The present study examined neural correlates of a simple broadband noise stimulus in primary auditory cortex (A1) of young and aged Fisher-Brown Norway (FBN) rats. Age-related changes in unit responses to broadband noise-bursts and spontaneous activity were simultaneously recorded across A1 layers using a single shank, 16-channel electrode. Noise bursts were presented contralateral to the left A1 at 80 dB SPL. Aged A1 units displayed increased spontaneous (29%), peak (24%), and steady state response rates (38%) than did young A1 units. This was true across all A1 layers, although age-related differences were significantly greater for layers I–III (43% vs 18%) than lower layers. There was a significant age-related difference in the depth and duration of post-onset suppression between young and aged upper layer A1 units. The present functional differences across layers were consistent with studies showing greatest losses of gamma-aminobutyric acid (GABA) markers in superficial layers of A1 and with anatomic studies showing highest levels of inhibitory neurons located in superficial cortical layers. The present findings were also consistent with aging studies suggesting loss of functional inhibition in other cortical sensory systems.

Gap detection procedures efficiently measured salicylate-induced changes in behavior that were consistent with the presence of tinnitus. In addition, the reliable, stronger responses at many frequencies after salicylate injections suggest the possibility of measuring a hyperacusis-like phenomenon using these methods.

Age-related hearing loss, presbycusis, can be thought of, in part, as a slow progressive peripheral deafferentation. Previous studies suggest that certain deficits seen in presbycusis may partially result from functional loss of the inhibitory neurotransmitter glycine in dorsal cochlear nucleus (DCN). The present study assessed age-related behavioral gap detection changes and neurochemical changes of postsynaptic glycine receptor (GlyRs) subunits and their anchoring protein gephyrin in fusiform cells of young (7-11 month) and aged (28-33 month) Fischer Brown Norway (FBN) rats. Aged rats showed significantly (20-30 dB) elevated auditory brainstem-evoked response thresholds across all tested frequencies and worse gap detection ability compared to young FBN rats. In situ hybridization and quantitative immunocytochemistry were used to measure GlyR subunit message and protein levels. There were significant age-related increases in the α1 subunit message with significant age-related decreases in α1 subunit protein. Gephyrin message and protein showed significant increases in aged DCN fusiform cells. The pharmacologic consequences of these age-related subunit changes were assessed using [3H] strychnine binding. In support of the age-related decrease of α1 subunit protein levels in DCN, there was a significant age-related decrease in the total number of GlyR binding sites with no significant change in affinity. These age-related changes may reflect an effort to re-establish a homeostatic balance between excitation and inhibition impacting on DCN fusiform cells by down-regulation of inhibitory function in the face of an age-related loss of peripheral input. Age-related decrease in presynaptic glycine release results in altered subunit composition and this may correlate with loss of temporal coding of the aged fusiform cell in DCN. The previously reported role for gephyrin in retrograde intracellular receptor subunit trafficking could contribute to the α1 decrease in the face of increased message.