Biophysical and neural coding mechanisms of the ear

听觉是我们最基本的感官之一，在大多数动物的日常生活中起着至关重要的作用。例如，考虑到声音交流和听音乐的普遍性。听力障碍（例如，难以在嘈杂的环境中检测声音和/或跟随对话）是影响加拿大和全世界相当一部分人的生活质量的主要因素。COVID-19疫情进一步加剧了这种情况，口罩覆盖物使听力损失患者的沟通更加困难。健康的耳朵表现出显著的功能，既高度敏感（即，检测）并且选择性地（即，分解）声音。为了实现这一点，耳朵是一个积极的探测器：代谢能量被用来选择性地放大声音引起的运动。因此，健康的耳朵产生的声音可以在耳道中用灵敏的麦克风测量。这些信号被称为耳声发射（OAE）并且提供有价值的临床诊断（例如，新生儿听力筛查）和对活动耳的科学洞察。然而，由于哺乳动物耳蜗形态的复杂性和脆弱性，OAE的产生机制仍不清楚。因此，我们对人类耳蜗的了解主要来自对动物的侵入性研究。我的研究项目通过比较的方法研究听觉生物物理学和神经科学，利用动物王国中耳朵的形态多样性对我们有利。特别是，我们专注于Anolis蜥蜴。尽管缺乏哺乳动物听觉所必需的结构和特征，蜥蜴表现出相当的敏感性和选择性。因此，它们相对简单的耳朵可以提供一条重要的前进路径，用于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。该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振动测量。通过测试几个假设，将这些措施与它们确定灵敏度和选择性的能力联系起来，我们将更深入地了解我们活动耳朵的生物力学和神经编码。这些目标共同构成了一幅挂毯，让我们能够通过细胞协同性的透镜更好地理解听觉周边。在细胞协同性中，耳朵的许多部分协同工作，形成了与总和完全不同的东西。这种协同作用将使我们能够扩展我们对这个非凡的感觉系统的基本原理的知识，并为未来的转化研究奠定坚实的基础。此外，我的培训计划将促进多样性和促进包容性，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。

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.