Extension of NEURON simulator for simulation of reaction-diffusion in neurons

用于模拟神经元反应扩散的神经模拟器的扩展

• 批准号: 8073127
• 负责人: MICHAEL L HINES
• 金额: $ 39.78万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8073127
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DESCRIPTION (provided by applicant): Multiscale modeling for computational systems biology is growing in importance for neuroscience as well as for other areas of biomedical research. Integration of recent findings in computational cell biology and synapse function, in the context of neurons and neuronal networks, will require simulations that can incorporate reaction-diffusion modeling down to the level of genomic and proteomic expression. This will allow simulation of the complex biochemical interactions occurring in cell bodies, dendrites and spines. To do this, the NEURON simulator, designed to simulate electrophysiology, will require major extensions. The primary extension will involve addition of 3-dimensional intracellular spatial integration with registration to the existing multicompartment voltage integration. Additional extensions at front and back- ends will also be needed to make the new tools fully useable. This work will be done in collaboration with the VCell team at University of Connecticut Health Center, who will provide us with code from their integration procedures and will consult on development of additional viewers that will be needed for these complex simulations. This procedure will also ensure interoperability with the VCell simulator, other existing cell biology simulators that read and write SBML (Systems Biology markup-language), and NeuroML. The extensions to NEURON will be effected through the following Specific Aims. 1. Kinetic translation from other kinetic markup languages. 2. Implementation of 3-D intracellular reaction diffusion modeling. 3. Development of two primary driving projects: a. model of ALS-related mitochondrial transport dysfunction; b. model of chemical fluxes between spine and dendrite. 4. Dissemination of the new tools. Dissemination is of critical importance to ensure that the new tool is used by some of the more than 650 active NEURON users. We will also make efforts to encourage cell neurobiologists to incorporate both NEURON and VCell into their technique repertoire. The ready translation of models between these two major platforms, using the several hundred peer-review published simulations available, will encourage simulation reuse and speed development of new applications. PUBLIC HEALTH RELEVANCE: The enormous complexity of brain interactions makes understanding brain diseases such as Alzheimer disease, Parkinson disease and epilepsy more difficult than understanding diseases in other organs. Part of this complexity lies in the need to understand how the chemicals that underlie learning and memory and brain energy interact with the electrical signals that travel along nerve fibers. We will extend NEURON, one of the most widely used nerve and brain simulators, so that it simulates chemical reactions as well as electric signals and allow these two types of information to be combined to understand disease.

描述（由申请人提供）：计算系统生物学的多尺度建模对神经科学以及其他生物医学研究领域的重要性增长。 在神经元和神经元网络的背景下，计算细胞生物学和突触功能中最新发现的整合将需要模拟，以将反应 - 扩散建模纳入基因组和蛋白质组学表达水平。 这将允许模拟在细胞体，树突和棘突中发生的复杂生化相互作用。 为此，旨在模拟电生理学的神经元模拟器将需要大量扩展。 主要的扩展将涉及增加3维细胞内空间整合，并注册到现有的多区域电压整合。 还需要在前端和后端进行其他扩展，以使新工具完全可用。 这项工作将与康涅狄格大学健康中心的VCELL团队合作完成，该中心将为我们提供集成程序中的代码，并就这些复杂模拟需要的其他观众的开发咨询。 此过程还将确保与VCELL模拟器，读写SBML（系统生物学标记语言）和Neuroml的其他现有细胞生物学模拟器的互操作性。 神经元的扩展将通过以下特定目的实现。 1。来自其他动力学标记语言的动力学翻译。 2。实施3-D细胞内反应扩散建模。 3。开发两个主要驾驶项目： 与ALS相关的线粒体转运功能障碍的模型； b。 脊柱和树突之间的化学通量模型。 4。新工具的传播。 传播对于确保有650多个活跃神经元用户中的一些新工具至关重要。 我们还将努力鼓励细胞神经生物学家将神经元和VCELL纳入其技术曲目。 使用数百个同行审查已发布的模拟，这两个主要平台之间的模型的现成翻译将鼓励新应用程序的模拟再利用和速度开发。 公共卫生相关性：大脑相互作用的巨大复杂性使您了解诸如阿尔茨海默氏病，帕金森病和癫痫病等脑部疾病比了解其他器官中的疾病更加困难。 这种复杂性的一部分在于需要了解学习和记忆和大脑能量基础的化学物质如何与沿神经纤维传播的电信号相互作用。 我们将扩展神经元，即使用最广泛的神经和脑模拟器之一，以便模拟化学反应和电信号，并允许将这两种类型的信息组合在一起以了解疾病。