Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
基本信息
- 批准号:7859442
- 负责人:
- 金额:$ 27.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-07-17 至 2012-02-28
- 项目状态:已结题
- 来源:
- 关键词:AddressAdmission activityAdrenergic ReceptorAdultAdverse effectsAffinityAgeAm 80AmericanAmino Acid NeurotransmittersAnatomyAntihypertensive AgentsArchitectureAutonomic nervous system disordersBaroreflexBindingBiological ModelsBlood PressureBrainBrain StemCardiovascular systemCell physiologyCellsCessation of lifeChemicalsCitrullineClinical ResearchClonidineComplexDendritesDevelopmentDirect CostsDiseaseDistalDizzinessDopamineDrug Delivery SystemsElderlyEpinephrineFall preventionFinancial costForce of GravityFunctional disorderGlutamatesGoalsHomeostasisHospitalsHumanImidazoleImmunofluorescence ImmunologicInferiorInjection of therapeutic agentInjuryInterneuronsJointsLabelLeadLigandsLinkLiteratureLocationMediatingMethodsMixed Function OxygenasesMotorMovementNeural PathwaysNeuronsNeurotransmittersNitric OxideNorepinephrineNuclearNucleus solitariusOrganOrthostatic HypotensionOutputPathway interactionsPharmaceutical PreparationsPharmacotherapyPhaseolus vulgaris leucoagglutininPhenotypePhenylethanolamine N-MethyltransferasePopulationPosturePressoreceptorsPresynaptic TerminalsProcessRattusRattus norvegicusReflex actionRegulationRelative (related person)ReportingResearchSignal TransductionSiteSocietiesSourceSpinal CordSympathetic Nervous SystemSynapsesSystemTestingThoracic spinal cord structureTissuesTracerTraumaVertigoVestibular nucleus structurebaseblood pressure regulationevidence basefallsgamma-Aminobutyric Acidimidazoleacetic acid ribotideimmunoreactivityinterestmedial vestibular nucleusmoxonidineneurochemistryneuronal cell bodynoradrenergicreceptorresearch studyrilmenidineyoung adult
项目摘要
It is currently understood that arterial baroreceptors control sympathetic nervous system tone, while
vestibular end organs provide afferent input to a vestibulo-sympathetic reflex that normally augments the
compensatory baroreflex. However, the chemical anatomy, connectivity and synaptology of the neural
pathways underlying this integration remain largely unknown. The overall goal of the proposed project is to
identify the neurotransmitters and modulators involved in mediating vestibulo-autonomic synaptic interactions.
The four aims address the chemoanatomy and synaptology of these vestibular projections in adult rats and
evaluate the overall hypothesis that different transmitter/modulator signatures and distinct synaptic
architectural arrangements are utilized by vestibular projections to the caudal and rostral ventrolateral medulla
(CVLM and RVLM, respectively). Aim 1 is to identify the locations of vestibulo-medullary and medullo-
sympathetic projection neurons, determine the relative proportions of vestibular projections to CVLM and
RVLM, identify the primary amino acid neurotransmitter(s) utilized by these pathways and determine whether
these projections terminate on glutamatergic and/or GABAergic neurons in CVLM and RVLM. Aim 2 is to
determine whether vestibular terminals in CVLM and RVLM co-express IAA-RP and/or L-citrulline. Aim 3 is to
conduct a qualitative analysis of the main neurotransmitters and modulators of vestibulo-recipient cells in
RVLM and CVLM, to test the hypothesis that glutamatergic vestibular afferents terminate on interneurons and
on distal dendrites of GABAergic/IAA-RP-containing CVLM neurons, GABAergic and noradrenergic dendrites
in RVLM, and directly on the somata of glutamatergic/IAA-RP-containing RVLM neurons with direct projections
to the spinal cord. Aim 4 is to visualize and quantify parameters of vestibulo-sympathetic synaptology, and will
test the hypothesis that the synaptology of vestibular terminals in RVLM involves complex interactions among
multiple transmitter systems, whereas the synaptology of vestibulo-sympathetic terminals in CVLM reflects
direct axo-dendritic contacts with CVLM output neurons. Throughout the project, the vestibulo-sympathetic
pathways will be identified using anterograde and retrograde tract-tracing in tissue that will be further
processed using additional immunofluorescent tags to identify transmitters and modulators of interest.
Ultrastructural studies will employ immunogold labels to identify and quantify terminals and synaptic contacts.
These studies will characterize the neurotransmitters, modulators and synaptic articulations utilized by
vestibular projections to sympathetic pre-motor medullary neuron pools and will yield qualitative analyses and
quantitative estimates of parameters of their synaptic architecture. This information does not currently exist in
the literature, and is important for the development of evidence-based pharmacotherapeutics for the treatment
of vestibulo-autonomic disorders such as orthostatic hypotension, as well as the development of more specific
anti-hypertensive medications that do not elicit disabling vestibular side-effects such as dizziness and vertigo. Project Narrative - Holstein
Orthostatic hypotension and vestibular side effects of drugs targeting the sympathetic nervous system (e.g.
anti-hypertensive medications) impact large populations, especially the elderly. However, little is known about
the neurochemical organization of vestibulo-sympathetic pathways. This project will provide fundamental
information about the chemoanatomic and synaptic organization of vestibular projections to cardiovascular
neurons in the ventrolateral medulla, may suggest new drug therapies to ameliorate orthostatic hypotension and
intolerance, and may lead to the development of more specific anti-hypertensive medications that do not elicit
disabling vestibular side effects such as dizziness and vertigo.
目前的理解是,动脉压力感受器控制交感神经系统的张力,而
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Gay R Holstein其他文献
Gay R Holstein的其他文献
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{{ truncateString('Gay R Holstein', 18)}}的其他基金
A cellular basis for neurogenic orthostatic hypotension
神经源性直立性低血压的细胞基础
- 批准号:
8960461 - 财政年份:2015
- 资助金额:
$ 27.95万 - 项目类别:
Chemoanatomic changes associated with aging in vestibulo-sympathetic pathways
与前庭交感神经通路衰老相关的化学解剖学变化
- 批准号:
8107476 - 财政年份:2010
- 资助金额:
$ 27.95万 - 项目类别:
Chemoanatomic changes associated with aging in vestibulo-sympathetic pathways
与前庭交感神经通路衰老相关的化学解剖学变化
- 批准号:
8005718 - 财政年份:2010
- 资助金额:
$ 27.95万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
7844551 - 财政年份:2009
- 资助金额:
$ 27.95万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
8463844 - 财政年份:2008
- 资助金额:
$ 27.95万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
8662741 - 财政年份:2008
- 资助金额:
$ 27.95万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
7467791 - 财政年份:2008
- 资助金额:
$ 27.95万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
7570038 - 财政年份:2008
- 资助金额:
$ 27.95万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
8115655 - 财政年份:2008
- 资助金额:
$ 27.95万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
9306405 - 财政年份:2008
- 资助金额:
$ 27.95万 - 项目类别: