MECHANICS OF MOTION TRANSDUCTION BY THE SEMICIRCULAR CANALS IN THE TOADFISH

蟾蜍半规管运动传导机制

• 批准号: 6592817
• 负责人: RICHARD D RABBITT
• 金额: $ 16.33万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6592817
• 关键词: Osteichthyes; afferent nerve; biological signal transduction; biomechanics; cilium /flagellum motility; ear hair cell; electrical measurement; electrophysiology; endolymph; mathematical model; mechanical pressure; membrane potentials; model design /development; morphology; neural information processing; semicircular duct; sensory signal detection; surgery

The overall goal of this project is to develop a mathematical model to determine the dynamics of the semi circular canal cupula and endolymph in the toadfish, Opsanus tau. The model will incorporate detailed physiological and morphological data. We will apply the model to determine the micromechanical response of the cupula including the mechanical strain acting on sensory hair cell cilia resulting from rotation of the head and mechanical indentation of the membranous labyrinth. This will provide a means to describe the relationship between the mechanical response and presynaptic events associated with the afferent response. The work is motivated by recent evidence suggesting a causal relationship between the micromechanics, dendritic morphology and afferent dynamic response. Afferent response in the toadfish has been categorized in three broad classes -- low gain, high gain and acceleration. The type of dynamic response correlates well with the location and geometry of the afferent dendritic processes within the crista. Consistent with this data, theoretical work by Rabbitt and Damiano predicts a frequency dependent deflected shape of the cupula that reflects the increase in gain present in the afferent dynamic response. We will build upon this previous work to include the micromechanics of the cupula. The endolymph will be modeled as a viscous Newtonian fluid coupled to the deformable cupula. Mechanical behavior of the cupula, the crista and the hair cell cilia will be modeled as a combination of elastic and visco-elastic materials reflecting the geometry and constituents of the tissue ultrastructures. The micromechanical response will include the distribution of strain acting on individual hair cell cilia. Mechanical deformation will provide the input to a hair cell transduction model describing the nonlinear relationship between the mechanical strain and the receptor potential. This will be utilized to drive a stochastic model of the hair cell synaptic response, dendritic field transmission and spike generation. The complete model will allow us to address the afferent response dynamics from first principles and to describe the influence of the morphology on the response of individual afferents. Model predictions will be compared to collaborative experimental data at several stages in the transduction process. Collaborative experimental measurements of the cupula deflection, excitatory Post-synaptic potential and afferent response will drive the evolution of the model. Results are expected to help to distinguish the influence of adaptation and hair cell diversity from the influence of cupular micromechanics, synaptic response and passive dendritic summation. In addition to these fundamental results, we will also be able to address the influence of numerous end-organ related conditions such as genetic and acquired malformations of the labyrinth, metabolic disorders, and the response in microgravity.

该项目的总体目标是开发一个数学模型 确定半圆管管套和内淋巴的动力学 在蟾蜍中，Opsanus tau。该模型将包含详细的 生理和形态数据。我们将把模型应用到 确定吸盘的微机械响应，包括 作用于感觉毛细胞纤毛的机械应变 头部的旋转和膜的机械压痕 迷宫。 这将提供一种描述关系的方法 机械反应和突触前事件之间的关联 传入反应。这项工作的动机是最近的证据 表明微观力学、树突状结构之间存在因果关系 形态学和传入动态反应。传入反应 蟾鱼可分为三大类——低增益、高增益 增益和加速度。动态响应的类型与 传入树突状过程的位置和几何形状 嵴。 Rabbitt 和的理论工作与此数据一致 达米亚诺（Damiano）预测了与频率相关的吸顶偏转形状， 反映了传入动态响应中增益的增加。 我们将在之前的工作的基础上纳入微观力学 顶盖。内淋巴将被建模为粘性牛顿流体 耦合到可变形的吸盘。吸盘的机械行为 嵴和毛细胞纤毛将被建模为以下组合 反映几何形状的弹性和粘弹性材料 组织超微结构的组成部分。微机械响应 将包括作用于单个毛细胞的应变分布 纤毛。机械变形将为毛细胞提供输入 描述非线性关系的转导模型 机械应变和受体电位。这将用于 驱动毛细胞突触反应的随机模型，树突状 场传输和尖峰产生。完整的模型将允许 我们从第一原则和 描述形态对个体反应的影响 传入。模型预测将与协作预测进行比较 转导过程中几个阶段的实验数据。 顶盖偏转的协作实验测量， 兴奋性突触后 潜在和传入反应将推动模型的演变。 预计结果将有助于区分适应的影响 和毛细胞多样性的影响 微观力学、突触反应和被动树突求和。在 除了这些基本成果之外，我们还能够解决 许多终末器官相关条件的影响，例如遗传 以及获得性迷路畸形、代谢紊乱和 微重力响应。