Abstract
Sodium salicylate (NaSal), an aspirin metabolite, can cause tinnitus in animals and human subjects. To explore neural mechanisms underlying salicylate-induced tinnitus, we examined effects of NaSal on neural activities of the medial geniculate body (MGB), an auditory thalamic nucleus that provides the primary and immediate inputs to the auditory cortex, by using the whole-cell patch-clamp recording technique in MGB slices. Rats treated with NaSal (350 mg/kg) showed tinnitus-like behavior as revealed by the gap prepulse inhibition of acoustic startle (GPIAS) paradigm. NaSal (1.4 mM) decreased the membrane input resistance, hyperpolarized the resting membrane potential, suppressed current-evoked firing, changed the action potential, and depressed rebound depolarization in MGB neurons. NaSal also reduced the excitatory and inhibitory postsynaptic response in the MGB evoked by stimulating the brachium of the inferior colliculus. Our results demonstrate that NaSal alters neuronal intrinsic properties and reduces the synaptic transmission of the MGB, which may cause abnormal thalamic outputs to the auditory cortex and contribute to NaSal-induced tinnitus.
Highlights
Sodium salicylate (NaSal), an active metabolite of aspirin, is one of the most widely used analgesic, anti-inflammatory, and antipyretic drugs
Our previous work on slices of the auditory cortex demonstrated that NaSal reduced the inhibitory postsynaptic current (IPSC) [14] and selectively suppressed the current-evoked firing of GABAergic interneurons without affecting glutamatergic pyramidal neurons [15]
There was no difference between baseline and saline treatments (P.0.05) indicating that saline treatment had no effect on gap prepulse inhibition of acoustic startle (GPIAS) at these frequencies
Summary
Sodium salicylate (NaSal), an active metabolite of aspirin, is one of the most widely used analgesic, anti-inflammatory, and antipyretic drugs. Our previous work on slices of the auditory cortex demonstrated that NaSal reduced the inhibitory postsynaptic current (IPSC) [14] and selectively suppressed the current-evoked firing of GABAergic interneurons without affecting glutamatergic pyramidal neurons [15]. Both of these effects increase the excitability of the auditory cortex by altering the balance between excitation and inhibition. NaSal increases neuronal excitability in the rat hippocampus It does so by reducing GABAergic inhibition without affecting intrinsic membrane excitability in CA1 pyramidal neurons [18]. The ability of NaSal to elevate the excitability in the cerebral cortex (e.g., the auditory cortex and the hippocampus) raises a question of whether NaSal exerts the same effect in subcortical brain structures, which may be part of a neural network involved in the perception of tinnitus
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