Modeling the Brainstem Neural Mechanisms for the Respiratory Pattern Generation

呼吸模式生成的脑干神经机制建模

• 批准号: 0091942
• 负责人: Ilya Rybak
• 金额: $ 29.95万
• 依托单位: Drexel University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0091942&HistoricalAwards=false
• 关键词: Modeling; Brainstem; Neural; Mechanisms; Respiratory

The brain integrates and coordinates neural processing across multiple levels of organization to produce behavior. This project takes the neural control of breathing as a system for computational modeling of cross-level integration of cellular, network and systems neural mechanisms. The overall objective is to build a united multi-level model of neural control of respiration, within a uniform framework to incorporate existing data and current hypotheses on respiratory control. It remains controversial whether respiratory oscillation is produced primarily by endogenous cellular 'pacemaker' activity, or instead by properties of excitation and inhibition within a network circuit. This project models membrane activity for single respiratory neurons to investigate bursting activity; models the whole circuitry of the central pattern generator (CPG) network to investigate how connectivity can result in a steady respiratory rhythm with realistic firing patterns and changes from external perturbations; and elaborates the CPG model to generate a pacemaker-driven rhythm under simulated conditions. Mechanisms and conditions for the transition between pacemaker-driven and network-based states for generating rhythms are investigated in computational models and directly compared to experimental biological data from other laboratories. Results will clarify fundamental aspects of the important topic of respiratory control, may settle a current controversy, and will have an impact beyond basic neuroscience, eventually to biomedical work including control-systems analysis of physiology. The complex multi-scale approach is novel, and will provide valuable postdoctoral and student training.

大脑整合和协调跨多个组织层次的神经处理来产生行为。本项目将呼吸的神经控制作为一个系统，对细胞、网络和系统神经机制进行跨层次集成的计算建模。总体目标是在统一的框架内建立呼吸神经控制的统一多层次模型，以结合现有数据和当前关于呼吸控制的假设。呼吸振荡是否主要由内源性细胞“起搏器”活动产生，还是由网络回路内的兴奋和抑制特性产生，仍然存在争议。该项目模拟单个呼吸神经元的膜活性，以研究破裂活动；模拟中枢模式发生器（CPG）网络的整个电路，以研究连接如何导致具有真实放电模式和外部扰动变化的稳定呼吸节律；并详细阐述了在模拟条件下产生由起搏器驱动的心律的CPG模型。在计算模型中研究了起搏器驱动和基于网络的状态之间转换的机制和条件，并直接与其他实验室的实验生物学数据进行了比较。结果将澄清呼吸控制这一重要课题的基本方面，可能解决当前的争议，并将产生超出基础神经科学的影响，最终影响生物医学工作，包括生理学的控制系统分析。复杂的多尺度方法是新颖的，并将提供宝贵的博士后和学生培训。