Effects of salicylate on neural activity in cat primary auditory cortex

The mechanisms of tinnitus: Perspectives from human functional neuroimaging

“…In cat A1, quinine was shown to significantly increase the height of the peak of the correlation between the spontaneous activity recorded across separate electrodes (Ochi and Eggermont, 1997) in a dosedependent manner. In another study by Ochi and Eggermont (1996) a greater number of auditory neuron pairs showed significantly correlated firing after salicylate application in cat A1, however, the strength of the peak of correlation did not alter.…”

“…Given that an external sound stimulus is normally signalled in the auditory system by an increased rate of neural firing, it is plausible that TI is consequence of a pathological increase in the rate of spontaneous random firing which can be erroneously interpreted as sound. Of relevance for human neuroimaging studies, animal models of TI have reported increased spontaneous firing rate in neurons within inferior colliculus (e.g., Jastreboff and Sasaki, 1986;Willott et al, 1988;Chen and Jastreboff, 1995;Manabe et al, 1997;Salvi et al, 2000b), medial geniculate body (e.g., Wallhäuser-Franke, 1997;Wallhäuser-Franke et al, 2003) and auditory cortex (e.g., Ochi and Eggermont, 1996;Kenmochi and Eggermont, 1997;Eggermont and Kenmochi, 1998;Eggermont and Komiya, 2000;Seki and Eggermont, 2003;Noreña and Eggermont, 2003). In inferior colliculus, it has been shown that spontaneous activity changes do not necessarily occur in all of its subdivisions, but are most prominent in the central and external nuclei, in those neurons tuned to high (10-16 kHz) frequencies likely to correspond to the TI pitch in animals (Jastreboff and Sasaki, 1986;Chen andJastreboff, 1995, Willott et al, 1988).…”

Molecular aspects of tinnitus

“…The increase in spontaneous discharge rate found by Evans and Borerwe (1982) has quite frequently been interpreted as a correlate of tinnitus in the peripheral auditory system. However, one has to consider that especially in cat salicylic acid can cause non-specific toxic effects, an effect discussed in earlier papers (Chen and Jastreboff, 1995;Ochi and Eggermont, 1996;Muller et al, 2003). In cat pharmacokinetics of salicylate is different from humans and small rodents.…”

Sodium salicylate suppresses serotonin-induced enhancement of GABAergic spontaneous inhibitory postsynaptic currents in rat inferior colliculus in vitro

“…Available evidence suggests that SS may produce tinnitus through directly targeting neurons and synapses in the central auditory system. Such lines of evidence include: (1) salicylate concentrations in the cerebrospinal fluid of animal models with behavioral manifestation of tinnitus induced by SS can reach a high level up to 1-2 mM (Deer and Hunter-Duvar, 1982;Jastreboff et al, 1986;Silverstein et al, 1967); (2) in a brain slice preparation, SS significantly reduces evoked inhibitory postsynaptic currents in rat auditory cortex (Wang et al, 2006) and changes the spontaneous activity of inferior colliculus neurons (Basta and Ernst, 2004); (3) treatment with SS injection increases the amplitude of local field potentials recorded from the auditory cortex of unanaesthetized rats (Yang et al, 2007) and changes spontaneous firing rate in the secondary auditory cortex of anesthetized cats (Eggermont and Kenmochi, 1998;Ochi and Eggermont, 1996); (4) animal microPET imaging shows that SS increases metabolic activity in the central auditory structures (Paul et al, 2007). These lines of evidence prompt a need to further explore how SS targets the central auditory system at a cellular and synaptic level in order to understand the exact neural mechanisms in SS-induced tinnitus.…”