Biophysical and neural coding mechanisms of the ear

耳朵的生物物理和神经编码机制

• 批准号: RGPIN-2022-04783
• 负责人: Bergevin, Christopher
• 金额: $ 3.5万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=762931
• 关键词: Biophysical; neural; coding; mechanisms; ear

Hearing is one of our most basic senses and plays a critical role in the daily lives of most animals. For example, consider the ubiquity of vocal communication and listening to music. Hearing impairment (e.g., difficulty detecting sounds and/or following conversations in noisy environments) is a major factor affecting the quality of life for a significant fraction of people in Canada and all around the world. The situation has been further exacerbated by the COVID-19 pandemic, where mask coverings make communication more difficult for those with hearing loss. Healthy ears exhibit remarkable functionality, being both highly sensitive (i.e., detect) and selective to (i.e., decompose) sounds. To achieve this, the ear is an active detector: Metabolic energy is used to selectively amplify sound-induced motions. As a consequence, healthy ears generate sounds that are measurable in the ear canal with a sensitive microphone. These signals are known as otoacoustic emissions (OAEs) and provide valuable clinical diagnostics (e.g., newborn hearing screening) and scientific insight into the active ear. However, much remains unknown about OAE generation mechanisms due to the morphological complexity and fragility of the mammalian cochlea. As such, our knowledge about the human cochlea is primarily inferred from invasive work done with animals. My research program studies auditory biophysics and neuroscience by taking a comparative approach, using the morphological diversity of the ear across the animal kingdom to our advantage. In particular, we focus on the Anolis lizard. Despite the absence of structures and features commonly thought essential for mammalian hearing, lizards demonstrate comparable sensitivity and selectivity. Thereby, their relatively simpler ears can provide an essential path forward for shedding light upon the active mammalian ear and how the breakdown of key processes lead to hearing impairment. This proposal combines mathematical modeling and several non-invasive state-of-the-art measurement methods: otoacoustics, auditory evoked potentials, and laser Doppler vibrometry. By testing several hypotheses relating these measures to their ability to determine sensitivity and selectivity, we will gain much deeper insight into the biomechanics and neural coding of our active ears. Together, the proposed objectives form a tapestry that will allow us to better understand the auditory periphery through the lens of cellular cooperativity, where the many parts of the ear work together to form something wholly different from the sum. Such synergies will allow us to expand our knowledge about principles underlying this remarkable sensory system and set a solid foundation for future translational research. Further, my training program will promote diversity and foster inclusion, thereby establishing confidence in the voices of tomorrow's scientists and helping Canada become an international leader in auditory science.

听觉是人类最基本的感官之一，在大多数动物的日常生活中起着至关重要的作用。例如，考虑一下无处不在的声音交流和听音乐。听力障碍(例如，在嘈杂的环境中难以辨别声音和/或跟上对话)是影响加拿大和世界各地相当一部分人生活质量的主要因素。新冠肺炎疫情进一步加剧了这种情况，口罩使听力损失者的交流变得更加困难。健康的耳朵表现出非凡的功能，对声音高度敏感(即检测)和选择性(即分解)。为了实现这一点，耳朵是一个活跃的探测器：新陈代谢能量被用来选择性地放大声音诱导的运动。因此，健康的耳朵发出的声音可以通过灵敏的麦克风在耳道中测量到。这些信号被称为耳声发射(OAEs)，提供有价值的临床诊断(例如，新生儿听力筛查)和对活跃耳朵的科学洞察。然而，由于哺乳动物耳蜗的形态复杂性和脆弱性，对于OAE的产生机制仍有许多未知之处。因此，我们对人类耳蜗的了解主要是从动物身上进行的侵入性工作中推断出来的。我的研究项目采用比较的方法学习听觉生物物理学和神经科学，利用整个动物界耳朵的形态多样性对我们有利。我们特别关注Anolis蜥蜴。尽管蜥蜴缺乏通常被认为是哺乳动物听力所必需的结构和特征，但蜥蜴表现出了类似的敏感性和选择性。因此，它们相对简单的耳朵可以为揭示活跃的哺乳动物耳朵以及关键过程的崩溃如何导致听力障碍提供一条重要的前进道路。这一建议结合了数学建模和几种非侵入性的最先进的测量方法：耳声学、听觉诱发电位和激光多普勒测振法。通过测试将这些测量与它们确定灵敏度和选择性的能力相关的几个假设，我们将对我们活跃的耳朵的生物力学和神经编码有更深入的了解。总之，提出的目标形成了一幅挂毯，使我们能够通过细胞协作性的透镜更好地理解听觉外围，其中耳朵的许多部分一起工作，形成与总和完全不同的东西。这种协同效应将使我们能够扩大我们对这一非凡感觉系统背后的原理的了解，并为未来的翻译研究奠定坚实的基础。此外，我的培训计划将促进多样性和包容性，从而建立对未来科学家声音的信心，并帮助加拿大成为听觉科学的国际领导者。