Salicylate-induced peripheral auditory changes and tonotopic reorganization of auditory cortex

The neuronal mechanism underlying the phantom auditory perception of tinnitus remains elusive at present. For over 25 years, temporary tinnitus following acute salicylate intoxication in rats has been used as a model to understand how a phantom sound can be generated. Behavioral studies have indicated that the pitch of salicylate-induced tinnitus in the rat is approximately 16 kHz. In order to better understand the origin of the tinnitus pitch measurements were made at the levels of auditory input and output; both cochlear and cortical physiological recordings were performed in ketamine/xylazine anesthetized rats. Both compound action potentials and distortion product otoacoustic emission measurements revealed a salicylate-induced band-pass-like cochlear deficit in which the reduction of cochlear input was least at 16 kHz and significantly greater at high and low frequencies. In a separate group of rats, frequency receptive fields of primary auditory cortex neurons were tracked using multichannel microelectrodes before and after systemic salicylate treatment. Tracking frequency receptive fields following salicylate revealed a population of neurons that shifted their frequency of maximum sensitivity (i.e. characteristic frequency) towards the tinnitus frequency region of the tonotopic axis (∼16 kHz). The data presented here supports the hypothesis that salicylate-induced tinnitus results from an expanded cortical representation of the tinnitus pitch determined by an altered profile of input from the cochlea. Moreover, the pliability of cortical frequency receptive fields during salicylate-induced tinnitus is likely due to salicylate's direct action on intracortical inhibitory networks. Such a disproportionate representation of middle frequencies in the auditory cortex following salicylate may result in a finer analysis of signals within this region which may pathologically enhance the functional importance of spurious neuronal activity concentrated at tinnitus frequencies.

▶Evaluated salicylate-induced tinnitus in rats in periphery and cortex. ▶Peripheral measures revealed altered profile of sensory input. ▶New profile of input corresponded to tinnitus pitch. ▶Observed overrepresentation of tinnitus pitch in auditory cortex.