Role of olivocochlear efferents in age-related hearing dysfunction

项目总结： 与年龄相关的听力障碍是一个普遍的公共卫生问题，在我们的 对潜在的中枢神经机制的理解。我们研究的长期目标是 了解衰老和听力损失如何同时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障碍。的中心假说 建议的研究是，随着年龄的增长，神经调节反馈通路变得失调，尤其是 橄榄耳蜗(OC)传出，降低老化的大脑保护外周损伤的能力和 补偿减少的外设输入。在较年轻的成年人中，OC神经元保护免受破坏性声音的伤害， 增强噪声中声音瞬变的处理，增强听觉选择性注意。这些过程 在年老的听众中受到干扰，OC系统的功能障碍可能是一个促成因素。初级阶段 拟议研究的目标是调查与年龄有关的组织和功能的变化 OC通路定义了它们对传回大脑的传入感觉信号质量的影响，以及 揭示这些变化是如何导致与年龄相关的听觉障碍的。次要目标是了解如何 可以利用对OC神经元的遗传和环境操纵来防止与年龄相关的疾病 听觉缺陷。我们将以三个具体目标来追求这些目标1)量化与年龄相关的OC变化 噪声中神经元形态及其与耳蜗神经传入变性和听力的关系；2)量化 听觉接收和处理的OC传出调制感觉信号的年龄相关变化 脑干；3)确定增加OC的遗传和环境操作的保护作用 针对年龄相关性听力障碍的系统激活。我们的方法将集成多种技术来 了解橄榄耳蜗系统和年龄相关性听力下降之间的关系，包括 听觉脑干反应、单个单位生理学、行为学和定量解剖分析 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节的年龄相关变化。在未来，这些 通路可能被操纵以防止年龄相关性听力下降，并改善听力。 存在相互竞争的声音。

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.