Robust criticality in hair bundles

发束中的鲁棒临界性

• 批准号: 9269058
• 负责人: Andrew R. Milewski
• 金额: $ 4.9万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9269058
• 关键词: Address; Affect; American; Auditory; Automobile Driving; Behavior; Biological; Biophysics; Calcium; Categories; Cells; Cochlea; Country; Detection; Discrimination; Disease; Ear; Ensure; Evaluation; Exhibits; Exposure to; Feedback; Frequencies; Generic Drugs; Hair; Hair Cells; Hearing; Hearing Aids; Ion Channel; Loudness; Mechanics; Mediating; Modeling; Nature; Organ; Organelles; Performance; Pharmacology; Physiologic pulse; Process; Property; Public Health; Rana catesbeiana; Side; Signal Transduction; Stimulus; System; Training; Validation; Work; aged; biological systems; cellular transduction; design; driving force; experience; experimental study; hearing impairment; inhibitor/antagonist; insight; mathematical model; novel; operation; predictive modeling; pressure; receptor; response; simulation; sound

PROJECT SUMMARY One in eight Americans aged twelve years and older—roughly 30 million people—suffers some degree of hearing loss. Hearing loss is broadly characterized as conductive, sensorineural, or mixed. The second of these categories encompasses the majority of people with hearing impairment and most frequently results from damage to hair cells, the cells in our ears responsible for detecting sound waves. Addressing this significant public-health concern requires a thorough understanding of the healthy operation of the hair cell and its signal- detection apparatus, the hair bundle. Our sense of hearing boasts exquisite sensitivity, precise frequency discrimination, and a broad dynamic range. A dynamic instability known as a Hopf bifurcation is thought to underlie these impressive features. Systems that exhibit a bifurcation demonstrate a qualitative change in behavior when a parameter of the system reaches its critical value. In hair bundles, this parameter might be calcium concentration or the external load applied to the bundle. Crossing a Hopf bifurcation incites spontaneous oscillations in a previously quiescent system. Just before this transition, when the system is on the verge of oscillating, small-amplitude stimuli are greatly enhanced. Analogously to a public address system turned up to the point of instability, our hearing derives its impressive features from this phenomenon. However, this enhanced response can occur for only the narrow range of parameter values that poise the system near the bifurcation. As a result, minuscule changes in certain parameters can compromise a hair bundle’s ability to detect sound. This poses a challenge to biological systems: How can hair cells exert tight control over parameters to ensure operation in close proximity to the bifurcation? This study seeks to answer this question from a novel perspective. Rather than achieving precise control over parameters, hair cells may employ a mechanism that broadens the region of influence of the dynamical instability. By widening the range of parameter values over which it can attain the desired level of performance, such a mechanism would render signal detection by a hair cell more robust. Evaluation of this hypothesis will be undertaken by first developing mathematical models of hair cell dynamics endowed with the proposed mechanism. Validation of these models will then be sought experimentally by delivering a variety of mechanical stimuli to hair bundles. These experiments will provide a means both to interrogate hair bundles for specific behaviors predicted by the model, and to identify potential effectors of the proposed mechanism. In addition to furthering our insight into how hair cells robustly detect signals, this work will deepen our understanding of the mechanisms responsible for the loss of auditory acuity that we experience following exposure to excessively loud sounds.

项目摘要 十二岁以上的八分之一的美国人（大约3000万人）享用一定程度 听力损失。听力损失的特征是导电，感觉神经或混合。第二 这些类别包括大多数听力障碍的人 损坏毛细胞，我们耳朵中负责检测声波的细胞。解决这一重要的问题 公共卫生的关注需要彻底了解毛细胞的健康操作及其信号 - 检测设备，头发束。 我们的听觉具有独家灵敏度，精确频率歧视和广泛的动态 范围。被称为HOPF分叉的动态不稳定性被认为是这些令人印象深刻的特征的基础。 存在分叉的系统表明，当系统的参数 达到其关键价值。在发束中，此参数可能是钙浓度或外部负载 应用于捆绑包。跨越HOPF分叉刺激以前静止的振荡 系统。在此过渡之前，当系统处于振荡的边缘时，小振幅刺激是 大大增强。与公共广播系统相似，我们的听证会已经不稳定了 从这种现象中获得了令人印象深刻的特征。但是，只有 狭窄的参数值范围毒害分叉附近的系统。结果，微不足道的变化 某些参数可能会损害发束检测声音的能力。这对生物学构成了挑战 系统：毛细胞如何对参数进行严格的控制以确保靠近靠近的操作 分叉？ 这项研究试图从新颖的角度回答这个问题。而不是实现精确控制 在参数上，毛细胞可以采用一种拓宽动态影响区域的机制 不稳定。通过扩大参数值的范围，它可以达到所需的性能水平， 这样的机制将使毛细胞更强大地使信号检测。对此假设的评估将是 首先开发了毛细胞动力学的数学模型，并赋予了所提出的数学模型 机制。然后，将发现对这些模型的验证通过提供各种机械性能在实验中遭受痛苦 刺激头发束。这些实验将提供一种既质疑特定发束的手段 模型预测的行为，并确定所提出机制的潜在影响。此外 这项工作进一步进一步了解了毛细胞如何牢固地检测信号，这项工作将加深我们对 导致听觉敏锐度丧失的机制，我们经历了极度接触后经历的 大声的声音。