Mechanisms of signaling in otoconial organs

描述（由申请人提供）：项目概述。正常的行为和空间方向取决于来自内耳的前庭信号。前庭周围有两个主要的分支：半规管和耳锥体器官。前者已被深入研究。尽管对前庭中枢加工的研究越来越强调它们在控制姿势、凝视、空间定向和营养功能方面的重要性，但人们对耳锥体器官的了解却少得多。因此，我们迫切需要了解迷宫的这一重要分支。我们建议通过分析来自耳蜗主要器官——耳室的信号的机械和生物物理起源来解决这一需求。我们的实验准备是一只海龟，它是分析周围听觉和前庭机制的首要模型系统之一。这个多学科的倡议分析了从行为到细胞建模的水平上的细胞机制。它建立在我们目前的生物力学研究结果的基础上，这些研究已经产生了关于任何脊椎动物的胞体结构和力学的最详细的数据库。Aim 1使用迷宫的高速视频记录和核磁共振图像来量化在自由行为的动物中暴露的毛细胞的刺激。目的2和目的3结合实验力学与生物物理和计算分析来表征重要的机械和毛细胞对这些刺激的反应。Aim 4使用形态生理学、信息分析和建模来量化所产生的传入信号及其信息内容，将这些信号与毛细胞对相同刺激的反应进行对比，并检验关于脑室传入信号多样性起源的假设。因此，拟议的研究继续我们的努力，以建立第一个详细的，定量描述的机制，形成的电信号到CMS。的相关性。前庭功能障碍是就诊的常见原因。它可能特别致残，因此前庭功能障碍是一个重要的医疗、社会和经济问题。尽管其重要性，前庭系统，尤其是耳锥器官，远不如其他感觉系统了解得好。我们需要对耳廓器官功能的新认识来改进诊断和治疗策略。通过促进这方面的知识，拟议的研究直接关系到NIDCD的使命。

DESCRIPTION (provided by applicant): Project summary. Normal behavior and spatial orientation depend upon vestibular signals from the inner ear. There are 2 major subdivisions of the vestibular periphery: semicircular canals and otoconial organs. The former have been intensively studied. Otoconial organs are much less well understood, even though studies of central vestibular processing increasingly highlight their importance in control of posture, gaze, spatial orientation, and vegetative functions. Thus, there is a pressing need to understand this important subdivision of the labyrinth. We propose to address this need by analyzing the mechanical and biophysical origins of signals from a major otoconial organ, the utricle. Our experimental preparation is a turtle, 1 of the premier model systems for analyses of peripheral auditory and vestibular mechanisms. This multidisciplinary initiative analyzes utricular mechanisms at levels from behavior to cellular modeling. It builds on results from our current studies of biomechanics, which have yielded the most detailed data base on the structure and mechanics of the utricle available for any vertebrate. Aim 1 uses high-speed video recording and NMR images of the labyrinth to quantify the stimuli that utricular hair cells are exposed to in freely behaving animals. Aim 2 and Aim 3 combine experimental mechanics with biophysical and computational analyses to characterize important mechanical and hair cell responses to these stimuli. Aim 4 uses morphophysiology, information analysis, and modeling to quantify the resulting afferent signals and their information content, contrast these signals with hair cell responses to the same stimuli, and test hypotheses about the origins of signal diversity in utricular afferents. Thus, the proposed research continues our efforts to build the first detailed, quantitative description of the mechanisms that shape utricular signals to the CMS. Relevance. Vestibular dysfunction is a common cause of physician visits. It can be particularly disabling, and vestibular deficits are thus a significant medical, social, and financial concern. In spite of its importance, the vestibular system, and otoconial organs in particular, are far less well understood than other sensory systems. We need new knowledge of otoconial organ function to improve diagnosis and treatment strategies. By contributing to this knowledge, the proposed research is directly relevant to the mission of the NIDCD.