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 确定半圆形管库库和内淋巴的动力学 在蟾蜍中，Opsanus tau。该模型将结合详细 生理和形态数据。我们将将模型应用于 确定库库的微力响应，包括 机械应变作用于感官毛细胞纤毛的作用 头部旋转和膜的机械凹痕 迷宫。 这将提供一种描述关系的方法 在机械响应和突触前事件之间 传入响应。这项工作是由最近证据的动机 提出微力学，树突状的因果关系 形态和传入动态反应。传入响应 蟾蜍已经分为三个大型类别 - 低增益，高 增益和加速度。动态响应的类型与 传入的树突过程的位置和几何形状 克里斯塔。与这些数据，Rabbitt和Rabbitt的理论工作一致 达米亚诺（Damiano 反映传入动态响应中的增益增加。 我们将以先前的工作为基础，包括 库库。内晶将建模为粘性牛顿液 连接到可变形的库库。库库拉的机械行为， crista和毛细胞纤毛将被建模为 反映几何形状和弹性弹性材料 组织超微结构的成分。微机械响应 将包括作用在单个毛细胞上的菌株的分布 纤毛。机械变形将为毛孔提供输入 描述的转导模型 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 现场传输和尖峰产生。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。模型预测将与协作进行比较 在转导过程中的多个阶段的实验数据。 库布拉挠度的协作实验测量， 兴奋性后突触 潜在和传入的响应将推动模型的演变。 期望结果有助于区分适应的影响 和尿的多样性来自杯状的影响 微力力学，突触反应和被动树突总和。在 除了这些基本结果，我们还将能够解决 众多与终端相关条件（例如遗传条件）的影响 并获得了迷宫，代谢性疾病的畸形和 微重力的响应。