Animal Models of Tinnitus, Brain Imaging & Therapy

描述（由申请人提供）：该项目的总体目标是：(A)获得水杨酸盐或噪声暴露引起的耳鸣的行为估计，(B)通过MicroPET成像和电生理记录确定与水杨酸盐或噪声引起的耳鸣相关的神经活动变化，(C)确定耳鸣的行为、代谢和神经表现是否可以被NS1883抑制，NS1883是一种钾通道激动剂，似乎可以抑制水杨酸盐引起的耳鸣。将使用16通道电极阵列评估清醒动物的听觉皮层和下丘的自发和声音诱发神经活动。MicroPET成像结合FDG示踪剂将用于识别耳鸣期间听觉通路中代谢活动发生显著变化的区域。在Aim 1中，将测量高剂量水杨酸治疗后耳鸣的发作、恢复和音高。耳鸣的行为测量将与代谢活动和神经活动的变化相关。我们将确定NS1883是否可以抑制与水杨酸引起的耳鸣相关的行为、神经和代谢变化。在第二阶段，我们将评估高水平噪声暴露后耳鸣的发病、时间过程和音高。噪声性耳鸣的行为学测量与代谢活动和神经活动的变化有关。我们将确定NS1883是否能抑制与噪声性耳鸣相关的行为、神经和代谢变化。该项目将首次使用MicroPET成像来识别耳鸣动物模型中代谢活动的变化。该项目将显著促进我们对耳鸣相关的听觉通路代谢和神经变化的理解，并将评估一种新的钾通道激动剂在抑制水杨酸和噪声性耳鸣中的有效性。

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.