Biophysical Mechanisms Underlying Auditory Transduction

耳朵是一种非凡的探测器：它具有高度的灵敏度和选择性，并在超过12个数量级的大动态范围内运行。然而，对耳朵的直接生理学研究一直很困难，因此我们对耳朵中起作用的[复杂的基于细胞的]放大机制有很多不知道的地方。听力障碍通常是由于这些过程中的问题而引起的，并影响到相当一部分加拿大人的生活质量。幸运的是，我们可以利用耳朵的另一个非同寻常的特性：它不仅对声音做出反应，而且还会发出声音。这些声音被称为耳声发射(OAEs)，可以自发产生，也可以由外部刺激诱发，使用灵敏的麦克风可以在耳道内进行非侵入性测量。耳声发射在科学和临床方面都取得了巨大的成功(例如，听力障碍的筛查)，进一步的研究将有助于明确我们对耳朵放大背后的基本生物物理学的理解。 这项研究的目标是表征耳声发射的产生机制及其与耳朵感觉细胞如何将声音信息编码到大脑中的关系。该项目主要关注蜥蜴，并将实验与数学建模相结合，该项目的目标将解决目前处于基础听觉科学核心的几个基本问题。尽管与哺乳动物相比，蜥蜴耳朵的形态和生理相对简单，但它们分享了更复杂动物的许多共同功能特征(例如，低阈值、尖锐的调谐、健壮的耳声发射)。因此，蜥蜴耳朵的简单性在试图阐明许多被认为对脊椎动物听觉功能至关重要的潜在生物物理过程时可以成为我们的优势。因此，这里提出的工作最终将建立在我们对人类听觉功能的了解基础上，并有助于加拿大成为听力研究的国际领先者。

The ear is a remarkable detector: It is both highly sensitive and selective, and operates over a large dynamic range spanning more than 12 orders of magnitude. Direct physiological study of the ear however has been difficult, and thus there is much we do not know about the [complex array of cellular-based] amplification mechanisms at work in the ear. Hearing impairment commonly arises due to problems with these processes and affects the quality of life for a significant fraction of Canadians. Fortunately, we can make use of another extraordinary property of the ear: Not only does it respond to sound but emits it as well. These sounds, known as otoacoustic emissions (OAEs), can arise either spontaneously or be evoked by an external stimulus and are measurable non-invasively in the ear canal using a sensitive microphone. OAEs have been employed with great success in both scientific and clinical contexts (e.g., screening for hearing impairment) and further study will help crystallize our understanding of the fundamental biophysics underlying amplification in the ear. The aims of the study are targeted towards characterizing OAE generation mechanisms and their relationship to how the sensory cells of the ear encode sound information to the brain. Focusing primarily on lizards and combining experiment with mathematical modeling, the project's objectives will address several fundamental questions currently at the heart of basic auditory science. Despite the relative simplicity of their morphology and physiology when compared to mammals, lizard ears share many of the functional features common to more complex animals (e.g., low thresholds, sharp tuning, robust OAEs). Thereby, the simplicity of the lizard ear can be used to our advantage when trying to clarify many of the underlying biophysical processes believed crucial in vertebrate auditory function. Thus, the work proposed here will ultimately build on our knowledge of auditory function in humans and contribute towards Canada being an international leader in the study of hearing.