Animal Models of Tinnitus, Brain Imaging & Therapy

耳鸣动物模型、脑成像

• 批准号: 7850334
• 负责人: RICHARD J SALVI
• 金额: $ 6.41万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7850334
• 关键词: Acoustics; Affect; Agonist; American; Animal Model; Animals; Auditory; Auditory area; Auditory system; Behavioral; Behavioral Model; Biological; Brain; Brain imaging; Chronic; Communication impairment; Discipline of Nuclear Medicine; Dose; Effectiveness; Elderly; Electrodes; Generations; Goals; Hearing; Human; Image; Implant; Inferior Colliculus; Magnetic Resonance Imaging; Measures; Metabolic; Neurologic Manifestations; Noise; Noise Induced Tinnitus; Output; Peripheral; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Polydipsia; Positron-Emission Tomography; Potassium Channel; Psychophysics; Rattus; Recovery; Roswell Park Cancer Institute; Schedule; Science; Site; Subjective Tinnitus; System; Techniques; The Sun; Time; Tinnitus; Tracer; Up-Regulation; Yang; auditory pathway; awake; base; behavior measurement; conditioning; deafness; fluorodeoxyglucose; multidisciplinary; neurophysiology; pre-clinical; relating to nervous system; research study; salicylate; sound

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.

描述（由申请人提供）：该项目的总体目标是（A）获得对水杨酸盐或噪声暴露引起的耳鸣的行为估计，（B）利用 MicroPET 成像和电生理记录识别与水杨酸盐或噪声引起的耳鸣相关的神经活动变化，以及（C）确定是否可以通过以下方法抑制耳鸣的行为、代谢和神经表现： NS1883，一种钾通道激动剂，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 成像与 FDG 示踪剂相结合将用于识别听觉通路中显示耳鸣期间代谢活动显着变化的区域。在目标 1 中，将在高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引起的耳鸣相关的行为、神经和代谢变化。在目标 2 中，将在高强度噪声暴露后评估耳鸣的发作、时间过程和音调。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 是否可以抑制与噪音引起的耳鸣相关的行为、神经和代谢变化。该项目将是第一个使用 MicroPET 成像来识别耳鸣动物模型代谢活动变化的项目。该项目将显着增进我们对与耳鸣相关的听觉通路代谢和神经变化的理解，并将评估新型钾通道激动剂在抑制水杨酸和噪音引起的耳鸣方面的有效性。