Functional Integrity of the Aging Auditory Synapse

衰老听觉突触的功能完整性

• 批准号: 9151173
• 负责人: Anthony J Ricci
• 金额: $ 27.59万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9151173
• 关键词: Address; Age; Aging; Animal Model; Animals; Auditory; Auditory Brainstem Responses; Calcium; Calcium Channel; Cell physiology; Cochlea; Cochlear nucleus; Collaborations; Complex; Data; Deterioration; Early Intervention; Electric Capacitance; Electrophysiology (science); Elements; Ensure; Environment; Fiber; Frequencies; Functional disorder; Genetic; Glutamates; Goals; Hair Cells; Hearing; Homeostasis; Image; Immune; Inbred CBA Mice; Ion Channel; Lead; Maintenance; Measurement; Measures; Mechanics; Modeling; Molecular; Monitor; Mus; Mutation; Neuraxis; Noise-Induced Hearing Loss; Optics; Organ; Pathway interactions; Physiological; Presbycusis; Process; Property; Proteins; Quality of life; Research; Research Personnel; Signal Transduction; Site; Supporting Cell; Synapses; Synaptic Potentials; Synaptic Transmission; Synaptic Vesicles; System; Techniques; Technology; Testing; Time; Vesicle; Width; Work; abstracting; associated symptom; electrical property; electron tomography; ganglion cell; hearing impairment; loss of function; mouse model; nerve supply; novel; otoacoustic emission; postsynaptic; presynaptic; sensor; socioeconomics; sound; spiral ganglion; synaptic function; time use; trafficking; vesicular release; vibration

Abstract: Age related hearing loss (ARHL) has a major impact on quality of life of more than 70% of those over the age of 70. It is a growing problem with significant socioeconomic ramifications. The cause of ARHL is complex and likely involves both environmental and genetic factors. Symptoms associated with ARHL, specifically, the initial loss of ability to discriminate sound in a noisy environment that progress to high frequency loss that can further progress to lower frequencies over time, suggest a common vulnerability that is independent of the initial trigger. We are postulating that common to ARHL is an initial loss of hair cell afferent fiber synapses. Much as with noise induced hearing loss, we hypothesize a selective loss of high threshold fibers. We will test these hypotheses using multiple genetic mouse models of ARHL. Each will be monitored using whole animal auditory testing including auditory brainstem responses and distortion product otoacoustic emissions to document the time course of onset of ARHL in each model. Specific Aim 2 will evaluate synaptic maintenance and proteins associated with pre and postsynaptic elements to further characterize the temporal windows associated with hearing loss. Specific Aim 3 will use electrophysiological and optical technologies to measure synaptic vesicle release and trafficking, monitor calcium homeostasis and record postsynaptic properties synaptic potentials as well as electrical properties. Each aim is well integrated with the goals and techniques available from each of the other investigators on this proposal and together we shall identify a global framework in which to address this important translational problem.

摘要：与年龄相关的听力损失（ARHL）对更多生活质量有重大影响 超过70岁的人中有70％。这是一个日益严重的问题 社会经济的后果。 ARHL的原因很复杂，很可能涉及 环境和遗传因素。特别是与ARHL相关的症状 在嘈杂的环境中歧视声音的能力的最初丧失，该环境发展到很高 随着时间的流逝，频率损失可以进一步发展到较低的频率，建议 独立于初始触发的常见漏洞。我们假设 ARHL共有的是毛细胞传入纤维突触的初始丧失。和一样 噪声引起的听力损失，我们假设高阈值纤维的选择性损失。我们 将使用ARHL的多种遗传小鼠模型检验这些假设。每个都会 使用整个动物听觉测试（包括听觉脑干响应）监控 和失真产品耳声排放，以记录时间过程 每个模型中的ARHL。特定目标2将评估突触维护和蛋白质 与前突触和后元素相关，以进一步表征时间。 与听力损失相关的窗口。特定目标3将使用电生理学和 测量突触囊泡释放和运输的光学技术，监测钙 稳态和记录突触后特性突触电位以及电气 特性。每个目标都与可从中可用的目标和技术融为一体 对该提案的每个其他调查人员，我们将共同确定全球 解决这个重要的翻译问题的框架。