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

项目摘要 听力障碍是人类最常见的感觉异常之一，在美国影响近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。

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.