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Role of olivocochlear efferents in age-related hearing dysfunction

橄榄耳蜗传出神经在年龄相关性听力功能障碍中的作用

基本信息

批准号：
10434879
负责人：
Amanda M. Lauer
金额：
$ 39.4万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-09 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10434879
关键词：
Acoustic Nerve Acoustics Address Adult Affect Age Age of Onset Aging Alzheimer&apos s Disease Anatomy Auditory Auditory Brainstem Responses Auditory system Back Behavior Behavioral Brain Brain Stem Chronic Cochlea Cochlear nucleus Contralateral Data Denervation Ear Efferent Neurons Elderly Electrons Feedback Financial compensation Frequencies Functional disorder Future Genetic Goals Hair Cells Health Hearing Housing Human Immunohistochemistry Impairment Inner Hair Cells Knowledge Labyrinth Lateral Masks Measures Medial Mediation Morphology Mus Nerve Fibers Neurons Noise Outcome Outer Hair Cells Pathway interactions Peripheral Physiology Point Mutation Presbycusis Process Property Public Health Research Role Sensory Signal Transduction Stimulus Structure Synapses System Techniques Testing Up-Regulation age related aging brain auditory pathway auditory processing base cholinergic dementia risk experimental study genetic manipulation hearing impairment improved in vivo microscopic imaging mind control mouse model mutant nerve supply neuromechanism neuroregulation noise exposure optogenetics postsynaptic protective effect receptor response selective attention sound speech in noise young adult

项目摘要

Project Summary: Age-related hearing deficits are a prevalent public health problem, and major knowledge gaps remain in our understanding of the underlying central neural mechanisms. The long-term goal of our research is to understand how aging and hearing loss affects organization of central auditory pathways concurrent with peripheral degeneration, and how these changes contribute to hearing difficulties. The central hypothesis of the proposed research is that neuromodulatory feedback pathways become dysregulated with age, particularly the olivocochlear (OC) efferents, reducing the aging brain's capacity to protect against peripheral damage and compensate for diminished peripheral input. In younger adults, OC neurons protect against damaging sounds, enhance processing of acoustic transients in noise, and enhance auditory selective attention. These processes are disrupted in aging listeners, and dysfunction of the OC system is likely a contributing factor. The primary objectives of the proposed research are to investigate age-related changes in the organization and function of the OC pathways, define their effects on the quality of the afferent sensory signals sent back to the brain, and reveal how these changes contribute to age-related auditory deficits. A secondary goal is to understand how genetic and environmental manipulation of OC neurons can be leveraged to protect against age-related auditory deficits. We will pursue these goals with three Specific Aims 1) Quantify age-related changes in OC neuronal morphology and their relationship to cochlear afferent degeneration and hearing in noise; 2) Quantify age-related changes in the OC efferent-modulated sensory signal received and processed by the auditory brainstem; 3) Determine the protective effects of genetic and environmental manipulations to increase OC system activation against age-related hearing deficits. Our approach will integrate multiple techniques to understand the relationship between the olivocochlear system and age-related hearing decline, including the auditory brainstem response, single unit physiology, behavior, and quantitative anatomical analysis of peripheral and central components of OC neurons in aging mouse models. These studies will lead to a better understanding of age-related changes in brain-controlled modulation of sensory function. In the future, these pathways may be manipulated to protect against age-related hearing decline and improve hearing in the presence of competing sounds.

项目概要：与听力损失相关的听力障碍是一个普遍的公共卫生问题，在我们的国家，了解潜在的中枢神经机制。我们研究的长期目标是了解衰老和听力损失如何影响中枢听觉通路的组织，外周变性，以及这些变化如何导致听力困难。的中心假设提出的研究是神经调节反馈通路随着年龄的增长而失调，橄榄耳蜗（OC）传出神经，降低老化大脑保护周围损伤的能力，补偿减少的外围输入。在年轻的成年人中，OC神经元保护免受破坏性声音的伤害，增强噪声中的声学瞬变的处理，并增强听觉选择性注意。这些过程在年老的听众中被破坏，OC系统的功能障碍可能是一个促成因素。主这项研究的目的是调查与年龄有关的组织和功能的变化， OC通路，定义了它们对发送回大脑的传入感觉信号质量的影响，揭示了这些变化如何导致与年龄相关的听觉缺陷。第二个目标是了解 OC神经元的遗传和环境操纵可以用来防止年龄相关的听觉缺陷我们将通过以下三个具体目标来实现这些目标：1）量化OC中与年龄相关的变化神经元形态及其与耳蜗传入神经元变性和噪声中听力的关系; 2）定量年龄相关的变化，OC传出调制的感觉信号接收和处理的听觉脑干; 3）确定遗传和环境操作的保护作用，以增加OC 系统激活对抗年龄相关的听力缺陷。我们的方法将整合多种技术，了解橄榄耳蜗系统和年龄相关的听力下降之间的关系，包括听觉脑干反应，单单位生理学，行为，和定量解剖分析，衰老小鼠模型中OC神经元的外周和中枢成分。这些研究将导致更好的了解大脑控制的感觉功能调制中与年龄相关的变化。未来这些可以操纵这些通路，以防止与年龄相关的听力下降，并改善老年人的听力。竞争的声音。