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: 8335501
• 负责人: Walid Jalabi
• 金额: $ 6.2万
• 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/8335501
• 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

Project Summary 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.

项目摘要 听力障碍是人类最常见的感官异常之一，在美国有近3000万人受到影响。听力障碍是由几个致病过程引起的，包括结构和遗传缺陷、感染、环境暴露和创伤。对外周听觉系统(耳、耳蜗神经和听神经)的致病效应已经被很好地描述，并且已经建立了几个动物模型来研究它们。然而，由于缺乏研究中枢听觉系统正常和紊乱的胚胎发生的动物模型，导致对控制中枢听神经元的指定、分化、轴突靶向和营养相互作用的发育过程的了解不完全。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了解。 这项建议的总体目标是了解大脑形态发生的中断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，这将首次允许我们研究这些过程，因为它们与下丘(IC)和上橄榄复合体(SOC)神经元有关。我们希望从这些模型中获得的见解将告诉我们，听神经元发育中断如何导致人类听力障碍。