Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous System
哺乳动物结肠神经系统的全面结构和功能图谱
基本信息
- 批准号:9776992
- 负责人:
- 金额:$ 247.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-16 至 2020-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAffectAfferent NeuronsAmericanAnatomyAnimal ModelAnimalsAnusBloodCell CommunicationCell physiologyCellsChemicalsChronicClostridium difficileColitisColonColonic DiseasesConfocal MicroscopyConstipationDataDevelopmentDiarrheaDiseaseDiverticulitisEfferent NeuronsElectric StimulationElectrophysiology (science)EndocrineEndocrine systemEnteralEnteric Nervous SystemEpitheliumEsthesiaExonsExpression ProfilingFamily suidaeFiber OpticsFoundationsFunctional disorderGenesHigh PrevalenceHomeostasisHumanImageImmuneImmunohistochemistryInflammationInflammatory Bowel DiseasesInternationalInterstitial Cell of CajalInterventionIrritable Bowel SyndromeKnowledgeLasersLightMalignant NeoplasmsManometryMapsMeasurementMethodologyMethodsMicrodissectionMicroelectrodesMicroscopyModalityMolecularMorbidity - disease rateMotorMucous MembraneMusMuscleMuscle CellsNerveNerve FibersNervous system structureNeuraxisNeuroanatomyNeurogliaNeuronsOperative Surgical ProceduresOralOrganParkinson DiseasePathway interactionsPatientsPatternPelvisPhysiologicalPlayPopulationPotentiometryPropertyPublic HealthQuality of lifeRattusReceptor SignalingResearch PersonnelResolutionRoleSensorySignal TransductionSiteSpinalSpinal GangliaSpinal cord injurySystemSystems IntegrationTechniquesTechnologyThree-Dimensional ImageThree-Dimensional ImagingTissuesTransgenic OrganismsTraumaViralVisceralVisceral painage relatedanimal tissuebasecell motilitycostdesigneffective therapyelectric impedancehuman tissueimmune functionin vivoinnovationinterdisciplinary approachlaser capture microdissectionmolecular phenotypemortalitymotility disordermultidisciplinarynerve supplyneural circuitneurochemistryneuroimagingneuromuscular transmissionneuronal circuitryneuroregulationnovel strategiesnovel therapeutic interventionoptogeneticspain sensationreceptive fieldreceptorrelating to nervous systemresponsesensory systemtargeted treatmenttherapeutic targettooltranscriptome sequencingtransmission processvoltage sensitive dye
项目摘要
ABSTRACT
The colon is the site of a multitude of disorders which are leading causes of morbidity and mortality and of
significant financial burden. The colonic intrinsic (enteric) and extrinsic innervation play crucial role in regulating
the secreto-motor, endocrine, immune functions and pain sensation. There has been increasing understanding
of the neurochemical and electrophysiological properties, cell physiology, and functional roles of colonic enteric
neurons and their interaction with the parasympathetic, sympathetic and sensory systems during the past
decades. However, these data are derived largely from small animal studies and relevant knowledge in large
animals and humans is lagging, which has hampered the development of effective therapies. Recent advances
in cutting edge approaches including 3-D mapping, innovative viral tracing tools, and neuroimaging provide a
means to obtain detailed information on neural circuits and related functions in large animals and human tissues,
which has never been achieved before. The overall objective of the proposal is to provide a comprehensive and
detailed structural and functional mapping of the intrinsic and extrinsic innervation of various regions of the colon
in humans and the pig, as a relevant large animal model based on its structural and physiological similarities to
humans. Mice will be utilized for studies involving transgenic, optogenetics and viral tracing approaches. This
objective will be achieved by a concerted effort of world expert investigators who developed state-of-the art
neuroanatomical, molecular, electrophysiological and functional approaches. Preliminary data obtained by the
consortium team showed the feasibility to use CLARITY, high resolution confocal microscopy, viral tracing and
optogenetics to provide detailed mapping of extrinsic nerve fibers, enteric circuitries and the expertise to probe
human colonic enteric neurons electrophysiologically by fast and high resolution neuroimaging. In addition, the
design of new microelectrode array and fiber optic technology has allowed quantifying motor patterns in response
to nerve stimulation at a resolution level not attained before. The combined effort and multidisciplinary
approaches will fill the gaps in current knowledge on colonic intrinsic and extrinsic neuronal circuits and cell-cell
communication, especially in human tissues and pig, a large animal model ideally suited for translational
applicability to patients. These findings will set the foundation for understanding neurocircuitry in this organ and
will be critical for potential electroceutical interventions to treat colonic disorders.
摘要
项目成果
期刊论文数量(0)
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Mechanisms and therapeutic interventions of postoperative gastric ileus
术后胃肠梗阻的机制和治疗干预
- 批准号:
10383642 - 财政年份:2017
- 资助金额:
$ 247.51万 - 项目类别:
Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous System
哺乳动物结肠神经系统的全面结构和功能图谱
- 批准号:
10008153 - 财政年份:2017
- 资助金额:
$ 247.51万 - 项目类别:
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$ 247.51万 - 项目类别:
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