Mechanisms of signaling in otoconial organs

项目总结。正常的行为和空间方向取决于来自内部的前庭信号 耳朵。前庭外周有两个主要的分支：半规管和耳锥器。 前者已经得到了深入的研究。对耳锥体器官的了解要少得多，尽管 对中央前庭加工的研究日益突出了它们在控制姿势、凝视、 空间定向和植物功能。因此，迫切需要理解这一重要的 迷宫的细分。我们建议通过分析机械和生物物理来解决这一需求 信号起源于主要的耳锥器官--椭圆体。我们的实验准备是一只乌龟，一种 用于分析外周听觉和前庭机制的主要模型系统。这 多学科主动性在从行为到细胞建模的各个层面上分析椭圆化机制。它构建了 基于我们目前的生物力学研究的结果，这些研究已经产生了关于 任何脊椎动物都有的椭圆囊的结构和力学。Aim 1使用高速视频录制 以及迷路的核磁共振图像，以量化椭圆形毛细胞自由接触的刺激 表现得像动物一样。目标2和目标3将实验力学与生物物理和计算相结合 分析以表征重要的机械和毛细胞对这些刺激的反应。AIM 4用途 形态生理学、信息分析和建模，以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比较，并检验假设 关于椭圆形传入中信号多样性的起源。因此，拟议的研究继续我们的努力。 建立第一个详细的，定量描述的机制，塑造椭圆体信号到CMS。 关联性。前庭功能障碍是医生就诊的常见原因。它可以特别地使人无法工作， 因此，前庭缺陷是一个重要的医疗、社会和经济问题。尽管它很重要， 前庭系统，特别是耳锥器官，远不如其他感官了解得好。 系统。我们需要耳锥器官功能的新知识来提高诊断和治疗水平 战略。通过对这一知识的贡献，拟议的研究直接关系到 NIDCD。

Project summary. Normal behavior and spatial orientation depend upon vestibular signals from the inner ear. There are two 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, one 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.