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

职业：通过多传感器细胞外记录技术估计神经元的位置、大小和树突树形态

• 批准号: 1056105
• 负责人: Zoran Nenadic
• 金额: $ 42.02万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1056105&HistoricalAwards=false
• 关键词: CAREER; Estimation; Neuron; Position; Size

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.

1056105，涅纳第问题陈述。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。这些类型的记录是通过放置在单个神经元附近的电极进行的，已经表征了许多关于大脑功能的已知信息。近几十年来，这项技术已经发展到了这样的地步：多个电极，每个电极都配备了多个传感器，并集成在一个单一的微驱动设备中，可以独立地降低到大脑中的感兴趣区域。尽管取得了这些进展，但细胞外记录过程仍然乏味和耗时，限制了多电极和多传感器技术的全部潜力。控制电极移动、持续监测记录信号、评估记录质量以及重新调整电极位置以补偿组织迁移需要持续的人类监督。有效管理细胞外记录电极的一个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陷是，人们对正在记录其活动的神经元的特性知之甚少。由于大小、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。在上述局限性的驱使下，本提案试图利用先进的数学和工程技术来开发一种统计框架，以基于对神经元细胞外电位的多传感器测量来估计神经元的位置、大小和树状树的形态(形状)。然后，将首先使用详细的计算神经元模型对建议的框架进行计算测试，然后使用动物脑片进行实验测试。将对几种商用多传感器记录电极进行理论和实验比较，以评估神经元的位置、大小和树突树形态。智力上的功绩。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，并根据神经元的大小和形状进行实验分离。应该强调的是，在目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。这项研究还将导致制定多传感器记录电极的最佳设计标准。总而言之，通过汇集工程学、数学和神经科学的想法，这一跨学科研究计划将从根本上改变细胞外记录实验的进行方式，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S教育计划的中心目标是设计、实施和测试一套教育工具和措施，旨在解决美国工程教育今天和未来面临的问题。具体地说，他将加强生物医学工程专业学生的教育经验，帮助他们更好地准备迎接不断变化的全球工程环境带来的挑战。他还将促进K-12少数族裔学生的工程教育和追求工程职业生涯，并为他们的数学和科学教师的专业发展和留住做出贡献。更广泛的影响。成功实现拟议的研究计划将使科学家处于有利地位，解决神经科学中的许多悬而未决的问题，并从根本上促进对动物大脑的科学理解。它还可能深刻影响多传感器电极的设计和制造，最终导致具有卓越记录能力的电极。必要学习的要素将被整合到跨学科工程学生的教学和指导中，同时尊重他们不同的学习需求和风格。研究人员S的教育计划还将扩大女性和少数族裔等未被充分代表的群体在工程学领域的参与。除了促进K-12学生的工程教育和对工程职业的追求外，调查员还将积极参与高需求学区K-12数学和科学教师的专业发展。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来广泛传播，从而有助于提高整个社区的科学素养。