Salicylate-Induced Auditory Perceptual Disorders and Plastic Changes in Nonclassical Auditory Centers in Rats

Abstract

Previous studies have shown that sodium salicylate (SS) activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis. Physiologically, the treatment significantly enhanced sound-evoked neural activity in the striatum, amygdala, and hippocampus, but not in the cingulate. The enhanced sound evoked response could be linked to the hyperacusis-like behavior. Further analysis showed that the enhancement of sound-evoked activity occurred predominantly at the midfrequencies, likely reflecting shifts of neurons towards the midfrequency range after SS-treatment as observed in our previous studies in the auditory cortex and amygdala. The increased number of midfrequency neurons would lead to a relative higher number of total spontaneous discharges in the midfrequency region, even though the mean discharge rate of each neuron may not increase. The tonotopical overactivity in the midfrequency region in quiet may potentially lead to tonal sensation of midfrequency (the tinnitus). The neural changes in the amygdala and hippocampus may also contribute to the negative effect that patients associate with their tinnitus.

Inner Hair Cell Loss Disrupts Hearing and Cochlear Function Leading to Sensory Deprivation and Enhanced Central Auditory Gain

“…To our knowledge, no one has tested for evidence of hyperacusis in carbolpatin-treated chinchillas to determine if loudness intolerance is related to carboplatin-induced hyperactivity. However, we have found a striking correlation between salicylate-induced hyperactivity in the central auditory system of rats with behavioral evidence of loudness hyperacusis (Chen et al, 2014, 2015). While enhanced central gain can compensate for the reduced neural output of the cochlea, too much gain at low sound levels could contribute to tinnitus whereas excess gain at high levels may give rise to loudness hyperacusis.…”

Noise trauma induced plastic changes in brain regions outside the classical auditory pathway

“…The Str, which is involved in motor planning and movements, receives auditory inputs and can modulate the startle reflex (Bordi and LeDoux, 1992, Kodsi and Swerdlow, 1995). Sound-evoked neural activity in the Str is also greatly enhanced by sodium salicylate, an ototoxic drug that induces tinnitus and hyperacusis (Chen et al, 2014b). Although the neural correlates of tinnitus and hyperacusis have been extensively studied in the classical auditory pathway, there is growing awareness that non-classical auditory areas such as the amygdala and Str may contribute directly or indirectly to these aberrant perceptions (Jastreboff, 2007, Rauschecker et al, 2010, Chen et al, 2012).…”

Can Animal Models Contribute to Understanding Tinnitus Heterogeneity in Humans?

“…The effects of tinnitus were until recently (Chen et al, 2014, 2015) studied very differently in animal models compared to humans. First of all detecting tinnitus is straightforward in humans—one just has to ask, whereas in animals it has to be inferred from behavioral tests.…”

“…Recently, Salvi and colleagues have made a start on this by recording LFPs and carrying out resting state and connectivity (fMRI) recordings in anesthetized rats (Chen et al, 2014, 2015). Human research using neural spiking activity can only be done in pre-surgical conditions such as for relief of epilepsy, but so far only depth-recorded LFPs are have been obtained (Sedley et al, 2015).…”