The effect of noise trauma and high-frequency stimulation on thalamic sensory gating in rodents

Abstract

BackgroundThe medial geniculate body (MGB) of the thalamus plays a central role in tinnitus pathophysiology. Breakdown of sensory gating in this part of the auditory thalamus is a potential mechanism underlying tinnitus. The alleviation of tinnitus-like behavior by high-frequency stimulation (HFS) of the MGB might mitigate dysfunctional sensory gating. ObjectiveThe study aims at exploring the role of the MGB in sensory gating as a mandatory relay area in auditory processing in noise-exposed and control subjects, and to assess the effect of MGB HFS on this function. Methods Noise-exposed rats and controls were tested. Continuous auditory sequences were presented to allow assessment of sensory gating effects associated with pitch, binary grouping, and temporal regularity. Evoked potentials (EP) were recorded from the MGB and acquired before and after HFS (100 Hz). Results Noise-exposed rats showed differential modulation of MGB EP amplitudes, confirmed by significant main effects of stimulus type, pair position and temporal regularity. Noiseexposure selectively abolished the effect of temporal regularity on EP amplitudes. A significant three-way interaction between HFS phase, temporal regularity and rat condition (noise-exposed, control) revealed that only noise-exposed rats showed significantly reduced EP amplitudes following MGB HFS. Conclusion This is the first report that shows thalamic filtering of incoming auditory signals based on different sound features. Noise-exposed rats further showed higher EP amplitudes in most conditions and did not differentiate the temporal regularity. Critically, MGB HFS was effective in reducing amplitudes of the EP responses in noise-exposed animals. Highlights▪ EP findings indicate sensory gating in the MGB in rats. ▪ Noise exposure alters EP amplitudes in the MGB. ▪ HFS selectively suppresses EP responses in noise-exposed animals.Abbreviations deep brain stimulation (DBS), evoked potentials (EP), high-frequency stimulation (HFS), linear mixed-effects model (LMEM), medial geniculate body (MGB), sensory gating (SG)