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.

项目摘要：与年龄相关的听力缺陷是普遍的公共卫生问题，并且在我们的理解潜在的中央神经机制。我们研究的长期目标是了解衰老和听力损失如何影响中央听觉途径的组织外围变性以及这些变化如何导致听力困难。中心假设拟议的研究是，神经调节反馈途径随着年龄的年龄而失调，尤其是橄榄石（OC）的侵蚀，降低了衰老大脑防止外围损伤和补偿外围输入减少的减少。在年轻人中，OC神经元可以防止破坏性声音，增强噪声中声学瞬变的处理，并增强听觉选择性关注。这些过程在老龄化的听众中受到破坏，OC系统的功能障碍可能是一个促成因素。主要拟议研究的目标是调查与年龄相关的组织和功能的变化 OC途径定义了它们对传入感官信号质量的影响，揭示这些变化如何导致与年龄相关的听觉缺陷。第二个目标是了解如何可以利用OC神经元的遗传和环境操纵来预防与年龄有关的听觉缺陷。我们将以三个特定目标追求这些目标1）量化与年龄相关的OC的变化神经元的形态及其与人工耳蜗传入变性和噪声听力的关系； 2）量化在听觉上接收和处理的OC调节的感觉信号的年龄相关的变化脑干; 3）确定遗传和环境操纵的保护作用以增加OC 系统激活与年龄有关的听力缺陷。我们的方法将将多种技术集成到了解橄榄石系统与年龄相关的听力下降之间的关系，包括听觉脑干反应，单个单位生理，行为和定量解剖分析老化小鼠模型中OC神经元的外围和中央成分。这些研究将导致更好了解与年龄相关的感觉功能调制的变化。将来，这些可以操纵途径以防止与年龄相关的听力下降并改善听力竞争声音的存在。