Abstract
Tinnitus is proposed to be caused by decreased central input from the cochlea, followed by increased spontaneous and evoked subcortical activity that is interpreted as compensation for increased responsiveness of central auditory circuits. We compared equally noise exposed rats separated into groups with and without tinnitus for differences in brain responsiveness relative to the degree of deafferentation in the periphery. We analyzed (1) the number of CtBP2/RIBEYE-positive particles in ribbon synapses of the inner hair cell (IHC) as a measure for deafferentation; (2) the fine structure of the amplitudes of auditory brainstem responses (ABR) reflecting differences in sound responses following decreased auditory nerve activity and (3) the expression of the activity-regulated gene Arc in the auditory cortex (AC) to identify long-lasting central activity following sensory deprivation. Following moderate trauma, 30% of animals exhibited tinnitus, similar to the tinnitus prevalence among hearing impaired humans. Although both tinnitus and no-tinnitus animals exhibited a reduced ABR wave I amplitude (generated by primary auditory nerve fibers), IHCs ribbon loss and high-frequency hearing impairment was more severe in tinnitus animals, associated with significantly reduced amplitudes of the more centrally generated wave IV and V and less intense staining of Arc mRNA and protein in the AC. The observed severe IHCs ribbon loss, the minimal restoration of ABR wave size, and reduced cortical Arc expression suggest that tinnitus is linked to a failure to adapt central circuits to reduced cochlear input.
Highlights
Tinnitus is a brain disorder causally linked to noise-induced hearing loss, cochlear damage [1], and stress [2,3,4,5,6,7]
auditory brainstem response (ABR) thresholds for click-stimuli (Fig. 1B, Table 1A) and frequency-specific stimuli (Fig. 1C and D, Table 1A) revealed a permanent, though mild, threshold loss in all animals that increased with exposure duration (Table 1A)
The group of tinnitus rats exposed to 1.5 h had a significantly larger hearing loss than no-tinnitus rats (Table 1A, 18.2064.23; n = 5 for tinnitus rats), and individual animals in both no-tinnitus groups showed significant hearing loss at isolated low frequencies (Fig. 1 C, D, crossed circles), what raises the question how hearing loss for low and high frequencies might contribute to the generation of tinnitus
Summary
Tinnitus is a brain disorder causally linked to noise-induced hearing loss, cochlear damage [1], and stress [2,3,4,5,6,7]. Due to demographic changes and to increasing use of personal headsets, especially by young people [8], tinnitus is a cumulative challenge In both tinnitus patients and tinnitus animal models, cochlear damage has been suggested to be associated with subcortical and cortical hyperactivity [1,9,10,11,12,13,14]. Unlike most previous studies on tinnitus, we analyzed hearing-impaired animals which, based on their behavior, were separated into groups with and without tinnitus [23] These groups were compared for (i) the number of CtBP2/RIBEYEpositive particles in ribbon synapses of the inner hair cell (IHC) as a measure for deafferentation [24], (ii) the fine structure of the amplitudes of auditory brainstem response (ABR) waves that may reflect crucial differences in sound responses following decreased auditory nerve (AN) activity [25], and (iii) the expression pattern of the rapid immediate early gene Arc/Arg3.1 (activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1, for simplicity referred to as Arc) in the auditory cortex (AC)
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