Animal Models of Tinnitus, Brain Imaging & Therapy

DESCRIPTION (provided by applicant): The overall goals of this project are to (A) obtain behavioral estimates of tinnitus induced by salicylate or noise exposure, (B) identify the changes in neural activity associated with salicylate or noise-induced tinnitus using MicroPET imaging and electrophysiological recordings and (C) determine if the behavioral, metabolic and neural manifestations of tinnitus can be suppressed by NS1883, a potassium channel agonist that appears to suppress salicylate-induced tinnitus. Spontaneous and sound evoked neural activity will be assessed in the auditory cortex and inferior colliculus of awake animals using 16-channel electrode arrays. MicroPET imaging combined with FDG tracer will be used to identify regions in the auditory pathway that show a significant change in metabolic activity during tinnitus. In Aim 1, the onset, recovery and pitch of tinnitus will be measured following treatment with a high dose of salicylate. Behavioral measures of tinnitus will be correlated with changes in metabolic activity and neural activity. We will determine if NS1883 can suppress the behavioral, neural and metabolic changes associated with salicylate-induced tinnitus. In Aim 2, the onset, time course and pitch of tinnitus will be assessed after high level noise exposure. Behavioral measures of noise-induced tinnitus will be correlated with changes in metabolic activity and neural activity. We will determine if NS1883 can suppress the behavioral, neural and metabolic changes associated with noise-induced tinnitus. This project will be the first to use MicroPET imaging to identify changes in metabolic activity in animal models of tinnitus. The project will significantly advance our understanding of the metabolic and neural changes in the auditory pathway that are associated with tinnitus, and will evaluate the effectiveness of a new potassium channel agonist in suppressing salicylate and noise-induced tinnitus.