CAREER: Estimation of Neuron's Position, Size and Dendritic Tree Morphology via Multi-sensor Extracellular Recording Technology

1056105，Nenadic 问题陈述。细胞外记录一个或多个神经元的电活动已成为实验神经科学的首选方法。这些类型的记录，用一个电极放置在一个单独的神经元附近，已经描述了很多关于大脑功能的知识。近几十年来，这项技术已经发展到多个电极，每个电极配备多个传感器并集成在单个微驱动设备中，可以独立地降低到大脑内的感兴趣区域。尽管有这些进展，细胞外记录的过程仍然繁琐和耗时，这限制了多电极和多传感器技术的全部潜力。需要持续的人工监督来控制电极移动，连续监测记录的信号，评估记录质量，并重新调整电极位置以补偿组织迁移。有效管理细胞外记录电极的主要障碍是缺乏关于神经元相对于记录电极的相对位置和迁移趋势的信息。细胞外记录技术的另一个严重缺点是，对被记录活动的神经元的特性知之甚少。由于诸如大小、形状和类型等属性通常与神经元功能有关，因此未能根据这些参数分离神经元会导致解释错误。 研究计划。受上述限制的激励，该提议寻求使用先进的数学和工程技术来开发统计框架，以基于神经元的细胞外电位的多传感器测量来估计神经元的位置、大小和树突树形态（形状）。然后将测试所提出的框架，首先使用详细的计算神经元模型进行计算，然后使用动物脑切片进行实验。理论和实验比较他们的能力，估计神经元的位置，大小和树突树形态，将进行几个商业多传感器记录电极。 智力优势。所提出的框架将能够更有效地定位和引导电极，估计神经元的迁移趋势，并根据其大小和形状实验分离神经元。应该强调的是，在当前的细胞外记录实践中，关于记录的神经元的位置、迁移趋势、大小和类型的信息通常是不可用的。该研究还将导致多传感器记录电极的最佳设计标准的发展。总之，通过汇集工程，数学和神经科学的想法，这个跨学科的研究计划将从根本上改变细胞外记录实验的方式，同时解决神经元电极界面出现的重要问题。 教育计划。调查员的核心目标是什么？的教育计划是设计、实施和测试一种教育工具和措施，旨在解决美国工程教育现在和将来面临的问题。具体而言，他将提高生物医学工程专业学生的教育经验，帮助他们更好地应对不断变化的全球工程环境所带来的挑战。他还将促进工程教育和少数民族K-12学生的工程职业追求，并为他们的数学和科学教师的专业发展和保留做出贡献。 更广泛的影响。成功实现拟议的研究计划将使科学家处于一个非常有利的位置，以解决神经科学中的许多悬而未决的问题，并从根本上推进对动物大脑的科学理解。它还可能深刻地影响多传感器电极的设计和制造，最终导致电极具有上级记录能力。必要的研究元素将被整合到跨学科工程专业学生的教学和辅导中，同时尊重他们不同的学习需求和风格。那个调查员教育计划还将扩大妇女和少数民族等代表性不足的群体对工程的参与。除了促进工程教育和追求K-12学生的工程事业，调查员将积极参与K-12数学和科学教师在高需求学区的专业发展。最后，本科生和研究生都将参与拟议的研究和教育计划。他们的研究结果将通过及时发布数据、出版物、网络材料和数字图书馆而广泛传播，从而有助于提高整个社区的科学素养。

1056105, Nenadic Problem Statement. Extracellular recording of the electrical activity of one or more neurons has become the method of choice in experimental neuroscience. These types of recordings, performed with an electrode positioned near an individual neuron, have characterized much of what is known about brain function. In recent decades, this technology has progressed to the point where multiple electrodes, each equipped with multiple sensors and integrated within a single microdrive device, can be lowered independently into an area of interest within the brain. Despite these advances, the process of extracellular recording remains tedious and time consuming which limits the full potential of multi-electrode and multi-sensor technology. Constant human supervision is required to command the electrode movement, continuously monitor recorded signals, assess the quality of recording, and re-adjust the electrode position to compensate for tissue migrations. A major impediment to efficient management of extracellular recording electrodes is the lack of information about the relative position and migration trends of neurons with respect to recording electrodes. Another severe shortcoming of extracellular recording technology is that very little is known about the properties of neurons whose activities are being recorded. Since properties such as size, shape and type are often linked to neuronal function, failure to separate neurons according to these parameters leads to interpretative errors. Research Plan. Motivated by the above limitations, this proposal seeks to use advanced mathematical and engineering techniques to develop a statistical framework to estimate neuron's position, size and dendritic tree morphology (shape), based on multi-sensor measurements of neuron's extracellular potentials. The proposed framework will then be tested, first computationally, using detailed computational neuron models, and then experimentally, using animal brain slices. Theoretical and experimental comparison of their ability to estimate neuron's position, size and dendritic tree morphology, will be performed for several commercial multi-sensor recording electrodes. Intellectual Merit. The proposed framework will enable more efficient positioning and guidance of electrodes, estimation of neuron's migration trends, and experimental separation of neurons according to their size and shape. It should be emphasized that information on position, migration trends, size and type of recorded neurons, is generally unavailable in current extracellular recording practice. The study will also lead to the development of optimal design criteria for multi-sensor recording electrodes. In summary, by bringing together ideas from engineering, mathematics, and neuroscience, this interdisciplinary research plan will fundamentally transform the way extracellular recording experiments are conducted while addressing important problems arising at the neuron-electrode interface. Educational Plan. The central goal of the investigator?s educational plan is to devise, implement and test a educational tools and measures, designed to address the concerns engineering education in the US faces today and will face in the future. Specifically, he will enhance the educational experience of biomedical engineering students to help them better prepare for the challenges imposed by the changing global context of engineering. He will also promote engineering education and the pursuit of engineering careers in minority K-12 students and contribute to the professional development and retention of their math and science teachers. Broader Impacts. Successful realization of the proposed research plan will place scientists in an excellent position to tackle many open questions in neuroscience, and fundamentally advance scientific understanding of the animal brain. It may also profoundly influence the design and manufacturing of multi-sensor electrodes, ultimately leading to electrodes with superior recording capabilities. Elements of the requisite study will be integrated into the teaching and mentoring of interdisciplinary engineering students, while respecting their diverse learning needs and styles. The investigator?s educational plan will also broaden the participation of underrepresented groups such as women and minorities in engineering. In addition to promoting engineering education and the pursuit of engineering careers in K-12 students, the investigator will actively participate in the professional development of K-12 math and science teachers in high-need school districts. Finally, both undergraduate and graduate students will be involved in the proposed research and educational plans. Their findings will be disseminated broadly by a timely release of data, publications, web-based materials, and digital libraries, thereby contributing to the improvement of scientific literacy in the community at large.