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Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus–hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed. One in three adults over the age of 65 will experience a significant loss of hearing. This is often worsened by related conditions, such as: tinnitus, an unexplained constant buzzing or ringing sound; and hyperacusis, whereby everyday sounds are perceived as too loud or painful. Most hearing loss is caused by damage to the sound-sensitive cells within a structure in the inner ear called the cochlea. Some studies have also identified regions of the brain that show abnormal activity in people with tinnitus and hyperacusis. However, the results from different patients have often been inconsistent and sometimes contradictory, and so it remains unclear what exactly causes these conditions. To overcome this problem, Chen et al. made use of the fact that tinnitus and hyperacusis are common short-term side effects of certain drugs and measured the brain activity in rats before and after they were given one such drug. Before receiving the drug, the rats had first been trained to expect to receive a food pellet from the left side of their cage when they heard a steady buzzing sound. The rats were also trained to expect a food pellet from their right if they heard nothing at all. Shortly after receiving the drug, the rats often failed to respond correctly in the ‘quiet tests’ and behaved like they were already experiencing a constant buzzing sound, as would be expected if they had tinnitus. Further tests confirmed that the drug also triggered behavior in the rats that is typical of people with hyperacusis. Chen et al. then discovered that the drug treatment reduced the nerve signals that are sent from a rat's cochlea. Moreover, the drug treatment greatly increased the activity in response to sound within parts of the rat's brain; these and other parts of the brain also became overactive in drug-treated rats in the absence of sound. Finally, further experiments revealed that drug-treated rats had stronger connections between these brain regions than in normal rats. Chen et al. used these results to propose a model to explain the underlying causes of tinnitus and hyperacusis. However, because the drug treatment only induces short-term hearing impairment, further studies are needed to see if this model also applies when these conditions are long-term.

Southern Illinois University School of Medicine, Springfield, and Illinois College, Jacksonville Jennifer Parrish Southern Illinois University School of Medicine Contact author: Jeremy G. Turner, Department of Surgery/Otolaryngology Head and Neck Surgery, Southern Illinois University School of Medicine, Springfield, IL 62794-9629. E-mail: jturner{at}siumed.edu . Purpose: A variety of options for behavioral assessment of tinnitus in laboratory animals are available to researchers today. These options are briefly reviewed, followed by data suggesting that gap detection procedures might be used to efficiently measure acute, salicylate-induced tinnitus and possibly hyperacusis in rats. Method: Fischer Brown Norway rats ( n = 10) were given intraperitoneal injections of 350 mg/kg sodium salicylate on 2 consecutive days, and the effects on gap detection were observed across 9 different frequency bands. Pretest, posttest, and washout data were collected. An additional 4 rats were each given 4 different doses of sodium salicylate (0, 150, 250, and 300 mg/kg), and gap detection and prepulse inhibition were measured. Results: Significant gap detection deficits were observed from pre- to posttest that were consistent with tinnitus. Consistent gap detection deficits were found using broadband noise backgrounds, while significant improvements in responding to frequency-specific test bands were found. Similar effects were repeated in the dose response portion of the study. Conclusions: 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. Key Words: tinnitus, hyperacusis, behavior, animal models, salicylate CiteULike     Connotea     Del.icio.us     Digg     Facebook     Reddit     Technorati     Twitter     What's this?

Tinnitus has been identified as a potential contributor to anxiety. Thalamo-cortical pathway plays a crucial role in the transmission of auditory and emotional information, but its casual link to tinnitus-associated anxiety remains unclear. In this study, we explore the neural activities in the thalamus and cortex of the sodium salicylate (NaSal)-treated mice, which exhibit both hyperacusis and anxiety-like behaviors. We find an increase in gamma band oscillations (GBO) in both auditory cortex (AC) and prefrontal cortex (PFC), as well as phase-locking between cortical GBO and thalamic neural activity. These changes are attributable to a suppression of GABAergic neuron activity in thalamic reticular nucleus (TRN), and optogenetic activation of TRN reduces NaSal-induced hyperacusis and anxiety-like behaviors. The elevation of endocannabinoid (eCB)/ cannabinoid receptor 1 (CB1R) transmission in TRN contributes to the NaSal-induced abnormalities. Our results highlight the regulative role of TRN in the auditory and limbic thalamic-cortical pathways. Sodium salicylate enhances endocannabinoid signaling, reducing GABAergic activity in the thalamic reticular nucleus. This increases gamma oscillations in the auditory cortex and prefrontal cortex, causing hyperacusis and anxiety-like behaviors.