Chaotic Dynamics of Inner Ear Hair Cells

听力损失影响着美国约3000万患者。由于内耳毛细胞的损失或损伤可导致深度耳聋，因此重要的是要了解其正常功能的机制，作为未来临床治疗进展的先决条件。这项研究的目的是阐明这种生物传感器是如何工作的，从而有助于未来研究它是如何失败的。非线性过程和主动放大已被证明是听觉极端灵敏度的关键。虽然许多研究已经探索了放大的各种潜在机制，但确定性或随机噪声的作用相对较少受到关注。因此，该项目是对目前在该领域进行的大多数工作的补充，并可以提供一些关于听觉和前庭系统如何在波动存在的情况下实现灵敏度的缺失信息。这种方法需要结合实验和理论研究来解决这个长期开放的问题。PI建议将联合收割机教育工作与研究计划相结合，向本科生教授与生命系统物理学相关的主题。在以前课程的基础上，她将介绍一个新的课程，让学生接触到统计力学和非线性动力学在生物学中广泛的开放性问题的应用。她还建议举办新的研讨会，旨在汇集来自理论物理学不同领域的科学家和研究听觉系统的生物学家。内耳的毛细胞是生物传感器，可以检测空气或地面振动引起的位移，并将其转换为电信号。它们的反应能力关键取决于一个主动过程，这个过程放大了传入声音引起的振荡。主动过程的特征之一，毛细胞束，已被证明表现出极限环振荡，在没有任何输入的情况下的自发运动。PI假设先天运动表现出混沌行为，并建议测试混沌如何影响检测的灵敏度。牛蛙球囊的毛细胞的长记录将在体外获得，并从动态系统理论的分析工具将被应用到提取的李雅普诺夫指数，构建庞加莱映射，并估计柯尔莫哥洛夫熵特征的运动。然后，毛细胞将受到不同强度和持续时间的机械刺激，以观察外部信号如何影响混沌状态。药理学和电操纵也将被用来平衡细胞在不同的动力学状态。我们的目标是确定这种生物系统是否以及如何利用混沌来提高其检测灵敏度。对毛束被动力学性质的估计表明，其在水中的热波动应该比检测阈值高出近一个数量级。PI建议研究噪声在发束响应中的作用，特别是它是否有助于检测所施加的信号。她的目的是解释如何在浸入水介质中的系统中进行灵敏的机械检测，保持在室温或更高的温度下，因此会受到显着的热波动。该研究将深入了解听觉的基本机制，并为混沌在主动系统检测灵敏度中的作用提供一个通用模型。该项目由物理学系生命系统物理学项目和综合有机系统系神经集群联合支持。

Hearing loss affects about 30 million patients in United States. Since loss or damage to hair cells of the inner ear can lead to profound deafness, it is important to understand the mechanisms of their proper functioning, as a prerequisite to progress in future clinical treatments. This study is aimed at elucidating how this biological sensor works, knowing which can hence aid in future studies of how it fails. Nonlinear processes and active amplification have been shown to be key to the extreme sensitivity of audition. While many studies have explored the various potential mechanisms of amplification, the role of either deterministic or stochastic noise has received comparatively little attention. This project is hence complementary to most of the work currently performed in the field, and could provide some of the missing information on how the auditory and vestibular systems achieve the sensitivity in the presence of fluctuations. This approach requires a combination of experimental and theoretical studies to address this long-open problem. The PI proposes to combine educational efforts with the research program, to teach undergraduate students topics of relevance for the physics of living systems. Building on prior courses, she will introduce a new class that will expose students to the applications of statistical mechanics and nonlinear dynamics to a broad range of open questions in biology. She also proposes to launch new workshops, aimed at bringing together scientists from different fields of theoretical physics and biologists studying the auditory system.Hair cells of the inner ear are the biological sensors that detect displacements induced by air-borne or ground-borne vibrations and transduce them into electrical signals. Their responsiveness is crucially dependent on an active process that amplifies oscillations induced by the incoming sound. One of the signatures of the active process, hair cell bundles, have been shown to exhibit limit cycle oscillations, spontaneous motion in the absence of any input. The PI hypothesizes that the innate motility exhibits chaotic behavior, and proposes to test how chaos impacts the sensitivity of detection. Long recordings of hair cells of the bullfrog sacculus will be obtained in vitro, and analytic tools from dynamic systems theory will be applied to extract the Lyapunov exponents, construct Poincare maps, and estimate the Kolmogorov entropy characterizing the motion. The hair cells will then be subject to mechanical stimulation of varying intensity and duration, to observe how the chaotic regime is impacted by external signals. Pharmacological and electrical manipulation will also be used to poise the cells in different dynamical states. The goal is to determine whether and how this biological system harnesses chaos to enhance its detection sensitivity. Estimates of the passive mechanical properties of a hair bundle indicate that its thermal fluctuations in water should be almost an order of magnitude higher than the detection threshold. The PI proposes to study the role of noise in the response of hair bundles, and specifically whether it can aid in the detection of applied signals. She aims to explain how sensitive mechanical detection could be performed in a system immersed in an aqueous medium, maintained at room or higher temperatures, and hence subject to significant thermal fluctuations. The study will provide insight into the fundamental mechanism of hearing, as well as providing a general model for the role of chaos in the sensitivity of detection by an active system.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Neural Cluster in the Integrative Organismal Systems Division.