Using Biofluiddynamics to Interrogate the Spinal Circuitry Controlling Movements

使用生物流体动力学询问控制运动的脊髓回路

• 批准号: 1066575
• 负责人: Neelesh Patankar
• 金额: $ 32.87万
• 依托单位: Northwestern University
• 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: 2011-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1066575&HistoricalAwards=false
• 关键词: Using; Biofluiddynamics; Interrogate; Spinal; Circuitry

1066575PatankarSummary description: Deciphering the logic behind how neural circuits generate behavior is a fundamental question in neuroscience. Locomotion offers a unique opportunity to probe issues of neuronal organization because motor circuitry generates a measurable product ? movement. Thus, studies of neural circuits for movement can not only help understand how the nervous system functions in general, but can also help to repair the motor circuitry after it has been disrupted, either by injury or disease. To fully grasp how to address the clinical challenges of overcoming neuronal disease or injury, it is informative to look for solutions in natural processes. This proposal is focused on the fundamental science underlying this transformational vision. The NU team will concentrate on discovering and understanding the function of spinal motor circuitry of a model system: the zebrafish.Intellectual merit: A major drawback of modern computational models is considered to be that the patterns of connectivity among spinal neurons are largely assumed. With a large parameter space, the assumed neural circuitry in the computational models, that mimic natural behavior, may not be the actual circuitry in organisms. The NU team has designed a research approach based on the hypothesis that information about the required muscle forcing for movement can be used to discover the actual neural circuitry. Hence, instead of assuming any neural circuitry, they propose a novel inverse paradigm in which they will first identify the muscle forcing required to produce the observed swimming kinematics. Second, they will construct possible neural circuits that could lead to the predicted muscle forcing. Finally, they will use transgenic zebrafish lines to hunt for classes of neurons predicted by the modeling, but as yet unidentified. Transformational impact: This project will lead to the discovery of new classes of neurons and the related circuitry, and to a fundamental understanding of how neuronal activation leads to a sequence of events in which the muscle energy is focused and transformed into the translational kinetic energy of movement. These fundamental discoveries and insights will not be restricted to the zebrafish model system but will conceptually apply in general to vertebrates whose movements range from swimming to limbed locomotion.Broader impact: The PIs will develop new interdisciplinary courses. The work done in this proposal will be a crucial application example that will be introduced in a book on computational methods that the PI is writing. The PI is also developing a novel approach based on computer animation to teach the fundamental principles in his research field. These educational videos will be broadly distributed through the internet by using YouTube.

1066575Patankar摘要描述：破译神经回路如何产生行为背后的逻辑是神经科学中的一个基本问题。运动提供了一个独特的机会，以探讨问题的神经组织，因为运动电路产生一个可测量的产品？运动因此，对运动神经回路的研究不仅可以帮助了解神经系统的一般功能，而且还可以帮助修复因受伤或疾病而中断的运动回路。为了充分掌握如何应对克服神经元疾病或损伤的临床挑战，在自然过程中寻找解决方案是有益的。这一建议的重点是这一变革愿景背后的基础科学。NU团队将专注于发现和理解模型系统：斑马鱼的脊髓运动电路的功能。智力优点：现代计算模型的一个主要缺点被认为是脊髓神经元之间的连接模式在很大程度上是假设的。在大的参数空间下，模拟自然行为的计算模型中假设的神经回路可能不是生物体中的实际回路。NU团队设计了一种基于以下假设的研究方法，即有关运动所需肌肉力量的信息可用于发现实际的神经回路。因此，他们没有假设任何神经回路，而是提出了一种新的逆向范式，在这种范式中，他们将首先确定产生所观察到的游泳运动学所需的肌肉作用力。其次，他们将构建可能的神经回路，从而导致预测的肌肉力量。最后，他们将使用转基因斑马鱼品系来寻找模型预测的神经元类别，但尚未确定。转型影响：该项目将导致发现新的神经元和相关电路，并从根本上理解神经元激活如何导致肌肉能量集中并转化为运动的平移动能的一系列事件。这些基本的发现和见解将不仅限于斑马鱼模型系统，而且将在概念上适用于一般的脊椎动物，其运动范围从游泳到四肢运动。更广泛的影响：PI将开发新的跨学科课程。在这个提案中所做的工作将是一个重要的应用例子，将在PI正在编写的一本关于计算方法的书中介绍。PI还开发了一种基于计算机动画的新方法，以教授他研究领域的基本原理。这些教育视频将通过YouTube在互联网上广泛传播。