The Effect of Noise Trauma and Deep Brain Stimulation of the Medial Geniculate Body on Tissue Activity in the Auditory Pathway

Abstract

Tinnitus is defined as the phantom perception of sound. To date, there is no curative treatment, and contemporary treatments have failed to show beneficial outcomes. Deep brain stimulation has been suggested as a potential therapy for refractory tinnitus. However, the optimal target and stimulation regimens remain to be defined. Herein, we investigated metabolic and neuronal activity changes using cytochrome C oxidase histochemistry and c-Fos immunohistochemistry in a noise trauma-induced rat model of tinnitus. We also assessed changes in neuronal activity following medial geniculate body (MGB) high-frequency stimulation (HFS). Metabolic activity was reduced in the primary auditory cortex, MGB and CA1 region of the hippocampus in noise-exposed rats. Additionally, c-Fos expression was increased in the primary auditory cortex of those animals. Furthermore, MGB-HFS enhanced c-Fos expression in the thalamic reticular nucleus. We concluded that noise trauma alters tissue activity in multiple brain areas including the auditory and limbic regions. MGB-HFS resulted in higher neuronal activity in the thalamic reticular nucleus. Given the prominent role of the auditory thalamus in tinnitus, these data provide more rationales towards targeting the MGB with HFS as a symptom management tool in tinnitus.

Keywords: deep brain stimulation; medial geniculate body; tinnitus.

Figure 1

Representative low-power photomicrographs taken from coronal rat brain sections stained with COX. (A,B) auditory cortex; (C,D) medial geniculate body; (E,F) CA1 of the hippocampus. The upper and lower panels represent a noise-exposed and control animal, respectively. (G) Graphs show the mean optical density of regions that showed significant changes based on group factors (noise-exposed vs. control). p value < 0.05 was defined as significant level and is indicated by an (*). Note that only contralateral Au1 and bilateral CA1 showed significant changes. Scale bar = 500 µm. Au1, primary auditory cortex; dcw, deep cerebral white matter; GrDG, granular layer of dentate gyrus; MGB, medial geniculate body.

Figure 2

Representative photomicrographs were taken of rat brain sections containing the thalamic reticular nucleus (TRN) in OFF DBS and ON DBS conditions (A,B, respectively). The sections were immunohistochemically stained using an antibody raised against c-Fos. (C) The graphs show the cumulative data of the means and SEMs of c-Fos-positive cells in ON DBS and OFF DBS groups on the ipsilateral and contralateral sides to noise trauma. Note that only TRN showed a significant increase in c-Fos expression in the ON DBS group. p values < 0.05 were defined as significant, and *** represents p ≤ 0.001. Scale bar = 1000 and 500 in the overview and zoomed box, respectively. Abbreviations: Au1, primary auditory cortex; BLA, basolateral amygdala; CIC, the central part of inferior colliculus; D3V, dorsal third ventricle; DG, dentate gyrus; DRN, dorsal raphe nucleus; Ic, internal capsule; TRN, thalamic reticular nucleus.