Animal Models of Tinnitus, Brain Imaging & Therapy

描述(申请人提供)：这个项目的总体目标是(A)获得水杨酸盐或噪音暴露引起的耳鸣的行为估计，(B)使用microPET成像和电生理记录确定与水杨酸盐或噪音诱导的耳鸣相关的神经活动的变化，以及(C)确定NS1883是否可以抑制耳鸣的行为、代谢和神经表现，NS1883是一种钾通道激动剂，似乎可以抑制水杨酸盐诱导的耳鸣。将使用16通道电极阵列评估清醒动物的听觉皮质和下丘的自发和声音诱发的神经活动。MicroPET成像结合FDG示踪剂将被用来识别听觉通路中显示耳鸣期间代谢活动显著变化的区域。在目标1中，将在大剂量水杨酸盐治疗后测量耳鸣的发作、恢复和音调。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盐诱导的耳鸣相关的行为、神经和代谢变化。在目标2中，将评估高水平噪音暴露后耳鸣的发作、时间进程和音调。噪音引起的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是否可以抑制与噪声诱导的耳鸣相关的行为、神经和代谢变化。该项目将首次使用微型PET成像来识别耳鸣动物模型中代谢活动的变化。该项目将极大地促进我们对与耳鸣相关的听觉通路中的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盐和噪声性耳鸣方面的有效性。

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.