RUI: Structural and Dynamical Specializations of Axons that Enhance Neural Coincidence Detection

高度专业化的细胞在整个大脑中处理和传输信息。该项目旨在开发数学模型和理论，以阐明听觉系统中的神经元如何以精确的时间精度处理声音。该项目使用一个独创的建模框架，允许系统地和参数地控制神经元的棘波产生区域，该项目将探索听觉处理的一个重要阶段--听觉脑干中的神经元--编码声源的空间位置的结构、动力学和功能之间的关系。这些神经元是符合检测器-它们对输入的时间很敏感，并对几乎同时到达的输入做出最大反应。这项研究的一个方面是通过考虑神经元结构的病理变化如何降低听力损失患者的时间处理能力，从而为促进公共健康做出贡献。该项目的一个重要组成部分是对本科生进行数学和科学培训。学生们将参与独特的暑期研究体验，在数学和神经科学的交汇点上获得知识，并为这所仅限本科生的机构创造一个充满活力的研究环境。该项目开发了神经符合检测建模的新数学方法。第一个目标是发展胞体-轴突耦合的多间隔模型，以量化在沿轴突有多个棘波产生的神经结构中如何提高符合检测灵敏度。重点将放在创建低维模型(具有很少的空间间隔)上，这些模型保留了这些神经元的基本动力学特性，并阐明了棘波起始位置如何提高符合检测灵敏度。第二个目标是剖析神经元在高频信号中处理时间信息的动力学机制。这里的重点将是鸟类大脑中的符合探测器神经元。这些神经元对产生千赫兹频率的小幅度电压振荡的输入做出反应。这项工作的目标是发展新的数学理论来解释神经元如何以与固有神经元时间尺度相似或更快的速度从振荡中提取时间信息。第三个目标是评估(通过模拟)听力损失过程中轴突结构的病理变化如何降低人工耳蜗术的“电听力”情况下的符合检测灵敏度。通过在各种背景下研究神经符合检测，该项目将有助于对神经电路中的非线性神经动力学和时间处理的一般理解。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Highly specialized cells process and transmit information throughout the brain. This project aims to develop mathematical models and theory to illuminate how neurons in the auditory system process sounds with exquisite temporal precision. Using an original modeling framework that allows systematic and parametric control of spike-generating regions of neurons, the project will explore relations between structure, dynamics, and function in an important stage of auditory processing: neurons in the auditory brainstem that encode the spatial locations of sound sources. These neurons are coincidence detectors – they are sensitive to the timing of inputs and respond maximally to inputs that arrive with near simultaneity. One prong of the research contributes to the advancement of public health by considering how pathological changes in neuron structure may degrade temporal processing in individuals with hearing loss. An essential component of the project is the mathematical and scientific training of undergraduate students. Students will engage in unique summer research experiences, gain knowledge working at the interface of mathematics and neuroscience, and contribute to a vibrant research environment at an undergraduate-only institution.The project develops new mathematical approaches to modeling of neural coincidence detection. The first objective is to develop multi-compartment models of soma-to-axon coupling to quantify how coincidence detection sensitivity may be enhanced in neural structures with multiple sites of spike generation along the axon. The focus will be on creating low-dimensional models (with few spatial compartments) that preserve essential dynamical properties of these neurons and that elucidate how the site of spike initiation enhances coincidence detection sensitivity. The second objective is to dissect the dynamical mechanisms by which neurons process temporal information in high-frequency signals. The focus here will be on coincidence detector neurons in the brainstems of birds. These neurons respond to inputs that generate small amplitude voltage oscillations at kilohertz-scale frequencies. The goal of this work is to develop novel mathematical theory to account for how neurons extract temporal information from oscillations at speeds similar to, or faster than, intrinsic neuronal time-scales. The third objective is to assess (with simulations) how pathological changes to axon structure during hearing loss may degrade coincidence detection sensitivity in the case of "electric hearing" with cochlear implants. By investigating neural coincidence detection in a variety of contexts, the project will contribute to the general understanding of nonlinear neural dynamics and temporal processing in neural circuits.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.