Role of the inferior colliculus and superior olivary complex in the development a

下丘和上橄榄复合体在发育中的作用

• 批准号: 8253870
• 负责人: Walid Jalabi
• 金额: $ 6.32万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8253870
• 关键词: Ablation; Acoustic Nerve; Address; Affect; Animal Model; Auditory; Auditory system; Axon; Brain; Brain Stem; Cell Nucleus; Cochlea; Cochlear nucleus; Complex; Cues; Data; Development; Developmental Process; Ear; Embryonic Development; Environmental Exposure; Experimental Genetics; Genes; Genetic; Goals; Hearing problem; Human; Infection; Inferior Colliculus; Knockout Mice; Lateral; Lateral lemniscus; Maintenance; Maps; Medial; Midbrain structure; Modeling; Morphogenesis; Mutation; Neurons; Newborn Infant; Pathway interactions; Peripheral; Play; Population; Process; Role; Secondary to; Sensory; System; Systems Development; Techniques; Technology; Testing; Therapeutic Intervention; Time; Trauma; United States; Ventricular; axon guidance; gene function; hearing impairment; hindbrain; homeodomain; information processing; insight; lateral superior olive; mouse model; neurodevelopment; neuron development; neuron loss; novel strategies; recombinase; relating to nervous system; transcription factor; trapezoid body

DESCRIPTION (provided by applicant): Hearing impairment is one of the most common sensory abnormalities in humans, affecting nearly 30 million people in the United States. Hearing impairments are caused by several pathogenic processes including structural and genetic defects, infections, environmental exposures and trauma. Pathogenic effects on the peripheral auditory system (ear, cochlea, and auditory nerve) are well-described, and several animal models have been created to study them. However, a dearth of animal models to study normal and disrupted embryogenesis of the central auditory system has led to an incomplete understanding of developmental processes that control central auditory neuron specification, differentiation, axonal targeting, and trophic interactions. This, in turn, has limited our understanding of pathophysiological mechanisms and their consequences on the central auditory system. The overall goal of this proposal is to understand how disruptions of brain morphogenesis affect central auditory system development, connectivity and function. We have developed new mouse models that will, for the first time, allow us to study these processes as they relate to inferior colliculus (IC) and superior olivary complex (SOC) neurons. We expect that insights gained from these models will inform us as to how disruptions of auditory neuron development can contribute to human hearing disorders. PUBLIC HEALTH RELEVANCE: Hearing impairment is one of the most common sensory abnormalities in humans, affecting ~16.1% of the US population. This project addresses how developmental disruption of the central auditory system affects its overall organization, connectivity and function. Understanding the role of different components of the central auditory system will provide insight into how their loss of can cause hearing impairment and help in developing therapeutic interventions.

描述（由申请人提供）：听力障碍是人类最常见的感觉异常之一，影响了美国近3000万人。听力障碍是由几种致病过程引起的，包括结构和遗传缺陷、感染、环境暴露和创伤。对周围听觉系统（耳、耳蜗和听神经）的致病作用已得到充分描述，并已建立了几种动物模型来研究它们。然而，缺乏动物模型来研究中枢听觉系统的正常和中断的胚胎发生，导致对控制中枢听觉神经元的特化、分化、轴突靶向和营养相互作用的发育过程的不完全理解。这反过来又限制了我们对病理生理机制及其对中枢听觉系统的影响的理解。 这项研究的总体目标是了解大脑形态发生的破坏如何影响中枢听觉系统的发育、连接和功能。我们已经开发了新的小鼠模型，这将是第一次，使我们能够研究这些过程，因为它们涉及下丘（IC）和上级橄榄复合体（SOC）神经元。我们期望从这些模型中获得的见解将告诉我们听觉神经元发育的中断如何导致人类听力障碍。 公共卫生相关性：听力障碍是人类最常见的感觉异常之一，影响约16.1%的美国人口。这个项目解决了中央听觉系统的发育中断如何影响其整体组织，连接和功能。了解中枢听觉系统不同组成部分的作用将有助于深入了解它们的丧失如何导致听力障碍，并有助于制定治疗干预措施。