CENTRAL MECHANISMS RELATED TO TINNITUS

与耳鸣相关的中枢机制

• 批准号: 2014826
• 负责人: James A Kaltenbach
• 金额: $ 14.22万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2014826
• 关键词: aspartate; audiometry; auditory nuclei; avoidance behavior; choline acetyltransferase; gamma aminobutyrate; glutamates; glycine; hamsters; high performance liquid chromatography; loudness; microelectrodes; negative reinforcements; nerve threshold; neural information processing; neural plasticity; taurine; tinnitus

The main objective of this study is to further define tinnitus-like changes in the cochlear nucleus following exposure to intense sound. This study builds on the recent discovery that intense sound exposure at levels sufficient to induce tinnitus in humans leads to a dramatic increase in spontaneous neural activity in the dorsal cochlear nucleus of the hamster. The specific aims of this project are as follows: 1) To further define the time course of these increases, spontaneous activity will be recorded and systematically mapped as a function of location along the frequency axis for each of 5 postexposure recovery times from 2 days to 1 year. The locations of abnormal spontaneous activity will be marked iontophoretically with horseradish peroxidase. 2) The cochlear nuclei will then be analyzed to determine whether increases in spontaneous activity are accompanied by significant chemical changes. The concentrations of selected neurotransmitter candidates, neurotransmitter- associated enzymes, and neurotransmitter receptors will be assayed using high performance liquid chromatography and autoradiography. Changes in key neurotransmitter candidates and associated enzymes will be mapped histochemically along the tonotopic axis. Chemically altered areas will be identified and correlated with regions showing high spontaneous activity by reference to marks of horseradish peroxidase. 3) Electrophysiological recordings of spontaneous neural discharge rates, amplitudes, and temporal structure will be conducted at the single unit level to identify the neural correlates of tone-induced increases in spontaneous activity. 4) Psychoacoustic testing procedures will be employed to determine whether hamsters exposed to intense sound experience tinnitus, and if so, whether the tinnitus has a definable pitch. Findings from these experiments are expected to contribute to an understanding of central mechanisms of noise-induced tinnitus and pave the way toward the development of anti-tinnitus therapies.

本研究的主要目的是进一步定义耳鸣样症状 暴露于强烈声音后耳蜗核发生变化。这 研究建立在最近的发现之上，即强烈的声音暴露 足以引起人类耳鸣的水平会导致戏剧性的 耳蜗背核自发神经活动增加 仓鼠的。本项目的具体目标如下： 1） 进一步定义这些增加的时间过程，自发活动 将被记录并系统地绘制为位置函数 沿着频率轴，从 5 个暴露后恢复时间中的每一个 2天到1年。异常自发活动的位置将是 用辣根过氧化物酶进行离子电渗标记。 2) 耳蜗 然后将分析细胞核以确定是否增加 自发活动伴随着显着的化学变化。这 选定的候选神经递质的浓度，神经递质- 相关酶和神经递质受体将使用 高效液相色谱法和放射自显影术。变化 关键的候选神经递质和相关酶将被绘制出来 组织化学上沿音位轴。化学改变区域将 被识别并与表现出高自发性的区域相关联 参照辣根过氧化物酶的标记来确定活性。 3） 自发神经放电率的电生理记录， 幅度和时间结构将在单个单元进行 水平来识别音调引起的增加的神经相关性 自发活动。 4) 心理声学测试程序将 用于确定仓鼠是否暴露于强烈的声音 经历过耳鸣，如果有，耳鸣是否有可定义的 沥青。这些实验的结果预计将有助于 了解噪声引起的耳鸣的中心机制和铺路 抗耳鸣疗法的发展之路。