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.

这项研究的主要目的是进一步定义类似耳鸣 暴露于强烈声音后的人工耳蜗核的变化。这 研究以最近的发现为基础 足以在人类中诱导耳鸣的水平导致戏剧性 背部耳蜗核中自发神经活性的增加 仓鼠。该项目的具体目的如下：1） 进一步定义这些增加的时间过程，自发活动 将记录并系统地映射为位置的函数 沿着5个暴露后恢复时间中的每一个沿频率轴 2天到1年。异常自发活动的位置将是 用辣根过氧化物酶在离子phit虫上标记。 2）人工耳蜗 然后将分析细胞核，以确定是否增加 自发活性伴随着重大的化学变化。这 选定的神经递质候选者的浓度，神经递质 - 相关酶和神经递质受体将使用 高性能液相色谱和放射自显影。变更 将映射关键的神经递质候选和相关酶 在组织化学上，沿着体点轴。化学改变的区域将 被识别并与显示高自发的区域相关 通过参考辣根过氧化物酶标记的活动。 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位进行 识别音调引起的增加的神经相关性的水平 自发活动。 4）心理声学测试程序将是 用于确定仓鼠是否暴露于强烈的声音 体验耳鸣，如果是的话，耳鸣是否具有可定义的 沥青。这些实验的发现有望有助于 了解噪声引起的耳鸣和铺路的中心机制 开发抗染色疗法的方式。