Functional mapping of peripheral and central circuits for airway protection and breathing
Functional mapping of peripheral and central circuits for airway protection and breathing
批准号:
9301247
负责人:
DONALD C BOLSER
金额:
$265.43万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-25 至 2022-07-31
关键词:
Afferent NeuronsAfferent PathwaysAnimal ModelBehaviorBerylliumBiologicalBrainBrain StemBreathingCause of DeathCharacteristicsClinicalCollaborationsCommunicationComplexComputer SimulationComputersCoughingData FilesDiseaseElementsFeedbackFloridaFoundationsFunctional disorderFutureGasesGeneticGoalsHumanImpairmentInfectionInflammationInjuryInstitutionKnowledgeLaboratory ResearchLaryngectomyLarynxLungLung TransplantationMapsMental DepressionModalityModelingMotorMotor NeuronsMotor PathwaysNeural PathwaysNeuromechanicsNeuromuscular DiseasesNeuronal PlasticityNeuronsParalysedPathologyPathway interactionsPatientsPenetrationPeripheralPopulationProcessRecording of previous eventsReflex actionRegulationResearchResearch PersonnelRespirationRespiratory DiaphragmRespiratory physiologyRiskSensorySensory ReceptorsSpinalSystemTimeUniversitiesbasecentral nervous system injuryexperienceflexibilityfunctional plasticityin vivomotor disordermultidisciplinarynervous system disordernetwork modelsneurophysiologyneuroregulationnovelpatient populationprotective behaviorrelating to nervous systemrespiratoryresponsesensory feedbacksensory inputsensory mechanismspinal pathwaysuccessvocal cord
中文摘要
项目摘要
英文摘要
PROJECT ABSTRACT
The peripheral and central elements of the respiratory control system are not “fixed,” but undergo sustained
(neuroplastic) circuit reorganization to optimize function. This system can selectively utilize unique afferent
modalities and brainstem neural pathways to elicit episodic, coordinated airway protective behaviors (e.g.
cough, laryngeal adduction). Neuroplasticity is induced and undermined by inflammation, transient afferent
feedback, or CNS injury. As a result, breathing responses and airway protective behaviors are altered in ways
that can be adaptive or maladaptive. Existing models of the brainstem network and sensory control system
regulating breathing and airway protection do not explain changes in responses caused by neuroplasticity in
sensory, central integrating and efferent motor elements of the control system. This knowledge gap concerning
peripheral and central circuit-based processes increases the risk of inappropriate depression in breathing or
airway protective mechanisms by the neuromodulatory approaches being investigated in the SPARC initiative.
In this project, our goal is to understand fundamental principles of modulation and plasticity in afferent
pathways, brain networks and efferent systems controlling breathing and airway defense. The proposed
research will advance our understanding of circuits underlying respiratory control, laying the foundation for
future neuromodulatory strategies to normalize lung function in vulnerable clinical populations. We have
assembled a multidisciplinary team to utilize cutting edge genetic, neuroanatomical, neurophysiological and
computational modeling approaches to interrogate sensory, central and motor pathways of the respiratory
control system. Complementary studies will be performed in human patient populations with various forms of
sensory or motor dysfunction, including those with laryngectomy, double lung transplants and unilateral vocal
fold paralysis. Through these parallel studies, we will reveal fundamental mechanisms of respiratory
neuroplasticity resulting from injury, disease and/or afferent activation. New knowledge from peripheral and
central circuits in animal models and humans with pathologies will be used to create an iterative, computational
neuromechanical model that incorporates key elements of neuroplasticity. This model will enable predictions
as we develop neuromodulatory approaches to inform novel treatments for respiratory dysfunction. The project
is separated into four encompassing aims. Aim 1: Identify neuroanatomical and functional plasticity of lung
sensory mechanisms that regulate brainstem pathways for airway protective reflexes. Aim 2: Identify short
time-scale and sustained, circuit-based plasticity in airway motor, brainstem and spinal respiratory motor
pathways induced by sensory feedback (airway and diaphragm) and/or injury/disease. Aim 3: Investigate key
features of neuroplasticity in human respiratory behaviors. Aim 4: Develop a neuromechanical computational
model of the neural system controlling breathing and airway defense that incorporates plasticity induced by
sensory afferent feedback and injury/disease.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Central and Peripheral Regulation of Laryngeal Adduction
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批准号:10642800
-
项目类别:
-
资助金额:$68.61万
-
财政年份:2022
-
负责人:DONALD C BOLSER
-
依托单位:
Influence of Opioids on the Brainstem Respiratory Network
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批准号:10322091
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项目类别:
-
资助金额:$68.16万
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财政年份:2021
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负责人:DONALD C BOLSER
-
依托单位:
Influence of Opioids on the Brainstem Respiratory Network
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批准号:10546463
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项目类别:
-
资助金额:$68.16万
-
财政年份:2021
-
负责人:DONALD C BOLSER
-
依托单位:
Influence of Opioids on the Brainstem Respiratory Network
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批准号:10096723
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项目类别:
-
资助金额:$70.52万
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财政年份:2021
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负责人:DONALD C BOLSER
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依托单位:
Modeling the role of the NTS in the neurogenesis of airway defensive behaviors
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批准号:9458386
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项目类别:
-
资助金额:$1.39万
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财政年份:2017
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负责人:DONALD C BOLSER
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依托单位:
Functional mapping of peripheral and central circuits for airway protection and breathing
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批准号:9983440
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项目类别:
-
资助金额:$196.77万
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财政年份:2016
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负责人:DONALD C BOLSER
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依托单位:
Central Mechanisms of Airway Protection
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批准号:8130733
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项目类别:
-
资助金额:$55.41万
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财政年份:2010
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负责人:DONALD C BOLSER
-
依托单位:
Central Mechanisms of Airway Protection
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批准号:8539069
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项目类别:
-
资助金额:$52.81万
-
财政年份:2010
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负责人:DONALD C BOLSER
-
依托单位:
Central Mechanisms of Airway Protection
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批准号:7933398
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项目类别:
-
资助金额:$57.77万
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财政年份:2010
-
负责人:DONALD C BOLSER
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依托单位:
Central Mechanisms of Airway Protection
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批准号:8312579
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项目类别:
-
资助金额:$55.93万
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财政年份:2010
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负责人:DONALD C BOLSER
-
依托单位:
Neurogenesis of Cough
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批准号:7846159
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项目类别:
-
资助金额:$52.95万
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财政年份:2008
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负责人:DONALD C BOLSER
-
依托单位:
Neurogenesis of Cough
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批准号:7501050
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项目类别:
-
资助金额:$58.34万
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财政年份:2008
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负责人:DONALD C BOLSER
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依托单位:
Neurogenesis of Cough
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批准号:7685415
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项目类别:
-
资助金额:$52.7万
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财政年份:2008
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负责人:DONALD C BOLSER
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依托单位:
Regulation of the Cough Reflex
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批准号:6882692
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项目类别:
-
资助金额:$32.13万
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财政年份:2003
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负责人:DONALD C BOLSER
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依托单位:
Regulation of the Cough Reflex
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批准号:7056776
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项目类别:
-
资助金额:$31.36万
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财政年份:2003
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负责人:DONALD C BOLSER
-
依托单位:
Regulation of the Cough Reflex
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批准号:6736973
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项目类别:
-
资助金额:$31.52万
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财政年份:2003
-
负责人:DONALD C BOLSER
-
依托单位:
Regulation of the Cough Reflex
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批准号:6577115
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项目类别:
-
资助金额:$30.42万
-
财政年份:2003
-
负责人:DONALD C BOLSER
-
依托单位:
INTEGRATION OF CARDIOVASCULAR & RESPIRATORY INPUT
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批准号:3050083
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项目类别:
-
资助金额:$2.13万
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财政年份:1988
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负责人:DONALD C BOLSER
-
依托单位:
海外基金