Expression of c-fos in auditory and non-auditory brain regions of the gerbil after manipulations that induce tinnitus

Abstract

Subjective tinnitus is a phantom sound sensation that does not result from acoustic stimulation and is audible to the affected subject only. Tinnitus-like sensations in animals can be evoked by procedures that also cause tinnitus in humans. In gerbils, we investigated brain activation after systemic application of sodium salicylate or exposure to loud noise, both known to be reliable tinnitus-inductors. Brains were screened for neurons containing the c-fos protein. After salicylate injections, auditory cortex was the only auditory area with consistently increased numbers of immunoreactive neurons compared to controls. Exposure to impulse noise led to prolonged c-fos expression in auditory cortex and dorsal cochlear nucleus. After both manipulations c-fos expression was increased in the amygdala, in thalamic midline, and intralaminar areas, in frontal cortex, as well as in hypothalamic and brainstem regions involved in behavioral and physiological defensive reactions. Activation of these non-auditory areas was attributed to acute stress, to aversive-affective components and autonomous reactions associated with the treatments and a resulting tinnitus. The present findings are in accordance with former results that provided evidence for suppressed activation in auditory midbrain but enhanced activation of the auditory cortex after injecting high doses of salicylate. In addition, our present results provide evidence that acute stress coinciding with a disruption of hearing may evoke activation of the auditory cortex. We interpret these results in favor of our model of central tinnitus generation.

Alterations in Event Related Potentials (ERP) Associated with Tinnitus Distress and Attention

“…Using c-fos and 2-DG-experiments, Wallhäusser-Franke et al (2003 and Wallhäusser-Franke (1997) were able to show that after noise trauma and the application of ototoxic drugs in animals known to result in tinnitus such a salicylate, there was a reduction in auditory nerve and cochlear nucleus activity and an elevation of auditory cortex activity. Müller et al (2003) found a reduction in the mean spontaneous firing rate at the level of the auditory nerve after salicilate intoxication.…”

Phantom percepts: Tinnitus and pain as persisting aversive memory networks

“…In the case of tinnitus, enhanced activity of the amygdala is evidenced by c-fos expression in animal models (90,91), by source-localized electroencephalography (9), by positron emission tomography imaging (92), and by transient tinnitus diminution after suppression of the amygdalohippocampal complex by amytal (93). Hippocampal deficits have been documented in animal models of tinnitus and structural imaging in tinnitus patients has demonstrated a decrease in gray matter in the hippocampus (94).…”

Central neural activity in rats with tinnitus evaluated with manganese-enhanced magnetic resonance imaging (MEMRI)

“…One area receiving considerable attention is the auditory brainstem, in particular the dorsal cochlear nucleus (DCN) (Kaltenbach et al, 2005). However, the rostral brainstem, forebrain auditory structures, and nonauditory structures, such as the amygdala (AMYG), have also been implicated in the pathophysiology of tinnitus (Eggermont and Roberts, 2004;Lockwood et al, 2002;Norena et al, 2003b;Wallhausser-Franke et al, 2003). Evaluation of tinnitus mechanisms would be improved by examining relevant brain regions in subjects with a known and controlled etiology.…”