Nonlinear Dynamics of Auditory Hair Cells and Efferent Neurons

听觉毛细胞和传出神经元的非线性动力学

• 批准号: 2210316
• 负责人: Dolores Bozovic
• 金额: $ 55.23万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2210316&HistoricalAwards=false
• 关键词: Nonlinear; Dynamics; Auditory; Hair; Cells

The first level of processing of auditory information in the inner ear is performed by hair cells – specialized cells that detect sound and transmit information to the brain. These cells show extremely high sensitivity, responding to movements smaller than a nanometer. Further, they show a broad dynamic range, for they are able to withstand much larger deflections without permanent damage. It is still not understood how the auditory system achieves this sensitivity and how it can rapidly reduce it when exposed to a loud environment. It has been proposed that efferent neurons, which transmit information from the brain to the hair cells, serve a protective role that reduces hair cell damage induced by loud sound. However, thus far there is very little understanding of the physics behind this mechanism. The investigators in this project will measure directly how stimulation of efferent neurons affects the sensitivity of the hair cell, both in terms of its ability to detect weak signals and to withstand strong stimuli. Their goal is to compare the experimental findings to models based on nonlinear dynamics to explain how efference may provide a dynamic feedback system that controls the sensitivity of hearing.The inner ear contains an extremely sensitive mechanical detector, which routinely responds to nanoscale deflections. At the lowest perceptible levels, sound induces movements in the internal auditory organs that are as small as few Å. Meanwhile, the applied pressures that the auditory systems can withstand range over six orders of magnitude. A dynamic gain control mechanism which would modulate the sensitivity of detection by a hair cell would serve to explain how a system could simultaneously achieve such remarkable sensitivity while maintaining the requisite robustness. The goal of this project is to determine whether efferent neurons constitute the dynamic feedback mechanism which tunes the nonlinear properties of the hair cell. The investigators aim to explore how efferent activity affects the mechanical responsiveness of the sensory system by direct measurements performed in vitro on live and active hair cells under different levels of efferent activity. The investigators will compare the findings to theoretical predictions based on nonlinear dynamics theory, which has proposed that an internal control parameter self-tunes the system to the vicinity of a Hopf bifurcation. This study is therefore complementary to prior work in the field, and will serve to bridge areas previously studied in vivo and in vitro, as well as in theoretical models. The project will also provide important mentoring opportunities, as the PI aims to recruit graduate students from underrepresented groups through participation in the APS Bridge program.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

内耳中听觉信息的第一级处理是由毛细胞执行的，毛细胞是检测声音并将信息传输到大脑的专门细胞。这些细胞表现出极高的敏感性，对小于一纳米的运动做出反应。此外，它们显示出广泛的动态范围，因为它们能够承受更大的偏转而不会造成永久性损坏。目前还不清楚听觉系统是如何达到这种灵敏度的，以及当暴露在嘈杂的环境中时，它是如何迅速降低这种灵敏度的。有人提出传出神经元，从大脑传递信息到毛细胞，起到保护作用，减少由响亮的声音引起的毛细胞损伤。 然而，到目前为止，人们对这种机制背后的物理原理知之甚少。 该项目的研究人员将直接测量传出神经元的刺激如何影响毛细胞的敏感性，包括检测弱信号和承受强刺激的能力。他们的目标是将实验结果与基于非线性动力学的模型进行比较，以解释传出如何提供一个控制听觉灵敏度的动态反馈系统。 在最低的可感知水平上，声音会引起内部听觉器官的运动，这种运动小到只有几秒钟。同时，听觉系统所能承受的压力范围超过六个数量级。一个动态增益控制机制，它将调制毛细胞的检测灵敏度将用于解释一个系统如何能够同时实现这种显着的灵敏度，同时保持必要的鲁棒性。该项目的目标是确定传出神经元是否构成调节毛细胞非线性特性的动态反馈机制。研究人员的目的是探索传出活动如何影响感觉系统的机械反应，通过在不同传出活动水平下对活的和活跃的毛细胞进行体外直接测量。研究人员将把研究结果与基于非线性动力学理论的理论预测进行比较，非线性动力学理论提出了一个内部控制参数将系统自调整到Hopf分叉附近。因此，这项研究是补充以前的工作在该领域，并将有助于桥梁领域以前研究在体内和体外，以及在理论模型。该项目还将提供重要的指导机会，因为PI旨在通过参与APS Bridge计划从代表性不足的群体中招募研究生。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。