Development and Analysis of Neuronal Network Models of Respiratory Rhythms

呼吸节律神经网络模型的开发和分析

• 批准号: 0716936
• 负责人: Jonathan Rubin
• 金额: $ 20万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0716936&HistoricalAwards=false
• 关键词: Development; Analysis; Neuronal; Network; Models

Experiments have revealed the existence of a neural control system for respiration within the mammalian brain stem. Evidence indicates that this system maintains a stable respiratory rhythm and contributes to the adaptability of respiration to rapid changes in metabolic demand as well as to more gradual processes, such as aging and disease. The mechanisms through which this system operates, however, remain under intense investigation. This project will focus on central issues relating to the neural control of respiration, providing an analysis of the mechanisms that confer pacemaker capabilities on particular respiratory neurons and the way in which different groups of neurons interact, within the full mammalian respiratory network, to produce respiratory rhythms. The proposed research will lead to new results and experimental predictions about how specific network features, including intrinsic properties of neurons and characteristics of the interactions between them, contribute to the generation, and the modulation, of the rhythms that arise. In particular, results will suggest key network elements that may be targeted by internal feedback systems to modulate respiration in response to changing conditions and that may be compromised in pathological states.These advances will be achieved through the development and mathematical analysis of neuronal network models featuring varying levels of biological detail, constrained by experimental data. Significant portions of this work will proceed through collaborations with two experimental neuroscience labs. These interactions will provide direct access to experimental data and will lead to experimental testing of model predictions. The project will involve the contributions of graduate and undergraduate students, who will gain valuable research training in the course of their participation. Broader training impacts will be achieved through the incorporation of novel mathematical and biological results into graduate courses taken by students across multiple departments, the presentation of emerging ideas within a Math Biology Working Group, the supervision of research rotations by neuroscience students, and participation in interdisciplinary centers at the University of Pittsburgh.

实验已经揭示了哺乳动物脑干内呼吸的神经控制系统的存在。 有证据表明，该系统保持稳定的呼吸节律，并有助于呼吸适应代谢需求的快速变化以及更渐进的过程，如衰老和疾病。 然而，这一制度的运作机制仍在深入调查之中。该项目将重点关注与呼吸的神经控制有关的核心问题，分析赋予特定呼吸神经元起搏功能的机制，以及不同神经元群在整个哺乳动物呼吸网络中相互作用以产生呼吸节律的方式。拟议的研究将导致新的结果和实验预测，即特定的网络特征，包括神经元的内在特性和它们之间相互作用的特征，如何有助于产生和调节所产生的节奏。特别是，结果将建议的关键网络元素，可能有针对性的内部反馈系统，以调节呼吸响应不断变化的条件下，可能会受到损害的病理states.These进展将通过开发和数学分析的神经网络模型，具有不同层次的生物细节，实验数据的约束。 这项工作的重要部分将通过与两个实验神经科学实验室的合作进行。这些相互作用将提供对实验数据的直接访问，并将导致对模型预测的实验测试。该项目将涉及研究生和本科生的贡献，他们将在参与过程中获得宝贵的研究培训。 更广泛的培训影响将通过将新的数学和生物学成果纳入跨多个部门的学生所参加的研究生课程，数学生物学工作组内新兴思想的介绍，神经科学学生的研究轮换监督，以及参与匹兹堡大学的跨学科中心来实现。