Mechanisms of Swallow Control of Breathing

吞咽控制呼吸的机制

基本信息

批准号：
8290766
负责人：
PAUL W DAVENPORT
金额：
$ 72.16万
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/8290766
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. PUBLIC HEALTH RELEVANCE: Dysphagia commonly results in penetration and aspiration of bolus material into the lower airways, thereby contributing to a major cause of morbidity and mortality after a stroke or with neuromuscular disease. This project will increase our understanding of the basic neural mechanisms that integrate swallow and breathing and the respiratory-related neural mechanisms of dysphagia rehabilitation.

描述（由申请人提供）：该项目的目的是确定（i）呼吸神经网络如何在吞咽阶段产生吞咽呼吸模式控制呼吸和吞咽的神经元素的协调。我们的中心假设是，诱导的反射咽吞咽会通过燕子中央模式发生器（SCPG）重新配置呼吸中心模式发生器（RCPG）产生特定的吞咽模式。进一步假设，当前与吞咽困难的呼吸相关治疗方法通过补偿诱导的重新配置和控制上呼吸道，咽和呼吸道肌肉的SCPG和RCPG中的收敛神经元素的激活有效。 SCPG必须重新配置呼吸神经网络，因为在燕子期间还使用了许多用于控制咽部和喉部的肌肉。我们建议吞咽呼吸模式由动态组织到表达气道防御行为所需的调节元素的神经元组件控制。这些吞咽的行为控制组件由招募的SCPG神经元组成，这些神经元与RCPG招募了连通性，并重新配置了呼吸神经网络以产生吞咽呼吸模式。我们的整体方法是使用我们建立的气道防御反射模型同时记录多个脑干神经元。我们的自定义网络建模和仿真分析将使我们能够确定和预测SCPG和RCPG神经元素的募集，重新配置和输出模式，从而介导了吞咽呼吸模式以及吞咽的负载补偿调制。有3个具体目标。在特定的目标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。高级尖峰列车分析和指标将用于确定针对RCPG，SCPG和吞咽呼吸控制的这些神经元之间的合作放电模式。在特定的目标2中，我们将修改和测试燕子网络的模型。我们将在特定的脑干吞咽和呼吸神经元种群中纳入推断的功能相互作用，这些呼吸神经元种群通过与多个电极阵列的同时记录的尖峰列车分析确定。在特定的目标3中，我们将使用神经网络模型模拟来预测增加呼吸载荷对产生吞咽呼吸模式的募集和重新配置的神经元素的影响。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见解，了解这些控制系统所必需的预测以及可能恢复疾病中这些控制系统失败的潜在神经机制。公共卫生相关性：吞咽困难通常会导致推注材料进入较低气道的渗透和吸入，从而导致中风后或神经肌肉疾病后发病和死亡的主要原因。该项目将提高我们对整合吞咽和呼吸的基本神经机制以及吞咽困难康复的呼吸相关神经机制的理解。