Mechanisms of Swallow Control of Breathing

吞咽控制呼吸的机制

基本信息

批准号：
8722406
负责人：
PAUL W DAVENPORT
金额：
$ 3.31万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-21 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8722406
关键词：
Air Aspirate substance Behavior Behavior Control Biological Neural Networks Bolus Infusion Brain Stem Breathing Computer Simulation Custom Deglutition Deglutition Disorders Disease Dorsal Electrodes Elements Esophagus Exhibits Failure Felis catus Financial compensation Food Gagging Generations Goals Health Indium Larynx Mediating Metric Modeling Morbidity - disease rate Motor Muscle Neural Network Simulation Neuromuscular Diseases Neurons Oral cavity Outcome Output Pattern Penetration Pharyngeal structure Phase Population Recruitment Activity Reflex action Regulatory Element Rehabilitation therapy Research Project Grants Respiration Respiratory Muscles Sensory Stroke System Techniques Testing Therapeutic Tongue Training base central pattern generator computational network modeling in vivo insight models and simulation mortality muscle strength network models neural patterning neuromechanism pharyngeal patterning pharynx muscle relating to nervous system research study respiratory strength training treatment effect treatment strategy

项目摘要

DESCRIPTION (provided by applicant): The goal of this project is to determine (i) how the respiratory neural network generates the swallow-breathing pattern during the pharyngeal phase of swallowing, (ii) iterative computational modeling and simulation analysis testing model-based predictions on the recruitment, reconfiguration and output pattern of the neural elements that mediate the swallow-breathing pattern and (iii) mechanisms for induced load compensation modulation and coordination of neural elements that control breathing and swallow. Our central hypothesis is that induced reflex pharyngeal swallow generates a specific swallow-breathing pattern by swallow central pattern generator (sCPG) reconfiguration of the respiratory central pattern generator (rCPG). It is further hypothesized that current breathing-related treatments for dysphagia are effective by compensation induced reconfiguration and activation of convergent neural elements in sCPG and rCPGs that control upper airway, pharyngeal and respiratory muscles. The sCPG must reconfigure the respiratory neural network because many of the muscles used for control of the pharynx and larynx during breathing are also used during swallow. We propose that the swallow-respiratory pattern is controlled by neuronal assemblies dynamically organized into regulatory elements required for the expression of airway defensive behaviors. These behavioral control assemblies for swallow are composed of recruited sCPG neurons that exhibit recruited connectivity with the rCPG and reconfigure the respiratory neural network to generate the swallow-breathing pattern. Our overall approach will be to simultaneously record multiple brainstem neurons using our well established cat model of airway defensive reflexes. Our custom network modeling and simulation analysis will enable us to determine and predict the recruitment, reconfiguration and output pattern of the sCPG and rCPG neural elements mediating the swallow breathing pattern as well as load compensation modulation of swallow. There are 3 Specific Aims. In Specific Aim 1, multiple neurons in the dorsal and ventral swallow and respiratory groups will be recorded simultaneously during breathing and swallow. Advanced spike train analysis and metrics will be used to determine cooperative discharge patterns among these neurons specific to the rCPG, sCPG and swallow control of breathing. In Specific Aim 2, we will revise and test our model of the swallow network. We will incorporate inferred functional interactions among specific brainstem swallow and respiratory neuronal populations identified from analyses of spike trains simultaneously recorded with multiple electrode arrays. In Specific Aim 3, we will use our neural network model simulation to predict the effect of increased respiratory loads on recruited and reconfigured neural elements generating the swallow-breathing pattern. This research project will provide new and directly relevant insights into the control and coordination of swallow breathing pattern, predictions necessary to understand these control systems and potential neural mechanisms that may rehabilitate the failure of these control systems in disease.

描述（由申请人提供）：该项目的目标是确定（i）呼吸神经网络如何在吞咽的咽阶段生成吞咽呼吸模式，（ii）迭代计算建模和模拟分析测试基于模型的预测介导吞咽呼吸模式的神经元件的募集、重新配置和输出模式，以及（iii）诱导负荷补偿调节和控制呼吸和吞咽的神经元件协调的机制。我们的中心假设是，诱导反射性咽部吞咽通过呼吸中枢模式发生器（rCPG）的吞咽中枢模式发生器（sCPG）重构产生特定的吞咽呼吸模式。进一步假设，当前与呼吸相关的吞咽困难治疗是通过补偿诱导的重新配置和激活控制上呼吸道、咽部和呼吸肌的 sCPG 和 rCPG 中的会聚神经元件而有效的。 sCPG 必须重新配置呼吸神经网络，因为在呼吸过程中用于控制咽部和喉部的许多肌肉也在吞咽过程中使用。我们认为吞咽呼吸模式是由动态组织成表达气道防御行为所需的调节元件的神经元组件控制的。这些吞咽行为控制组件由招募的 sCPG 神经元组成，这些神经元表现出与 rCPG 的招募连接，并重新配置呼吸神经网络以生成吞咽呼吸模式。我们的总体方法是使用我们完善的猫气道防御反射模型同时记录多个脑干神经元。我们的定制网络建模和模拟分析将使我们能够确定和预测介导吞咽呼吸模式以及吞咽负载补偿调节的 sCPG 和 rCPG 神经元的募集、重新配置和输出模式。有 3 个具体目标。在具体目标1中，在呼吸和吞咽过程中将同时记录背侧和腹侧吞咽和呼吸组的多个神经元。先进的尖峰序列分析和指标将用于确定这些神经元之间特定于 rCPG、sCPG 和吞咽呼吸控制的协作放电模式。在具体目标 2 中，我们将修改并测试我们的吞咽网络模型。我们将整合通过对用多个电极阵列同时记录的尖峰序列进行分析而确定的特定脑干吞咽和呼吸神经元群体之间推断的功能相互作用。在具体目标 3 中，我们将使用神经网络模型模拟来预测增加的呼吸负荷对生成吞咽呼吸模式的招募和重新配置的神经元件的影响。该研究项目将为吞咽呼吸模式的控制和协调提供新的、直接相关的见解、理解这些控制系统所需的预测以及可能恢复这些控制系统在疾病中的失败的潜在神经机制。