Excitatory neurotransmission in the ventral tegmental area following neuropathic injury
神经性损伤后腹侧被盖区的兴奋性神经传递
基本信息
- 批准号:10475635
- 负责人:
- 金额:$ 4.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-24 至 2023-03-23
- 项目状态:已结题
- 来源:
- 关键词:Absence of pain sensationAcuteAddressAffectAffectiveAmygdaloid structureAnimal BehaviorAnimalsAnteriorAreaAutomobile DrivingBehaviorBehavioralBrainBrain regionCell physiologyCellsComplexCoupledCuesDepressed moodDevelopmentDiseaseDistantDopamineDopamine ReceptorElectrophysiology (science)EmotionalEsthesiaExcitatory SynapseGlutamatesGoalsInjuryInterneuronsKnowledgeLabelLaboratory ResearchLeadLeadershipLearningLesionMeasuresMental DepressionModelingModificationMolecularMoodsMusNervous system structureNeuraxisNeurobiologyNeuronal PlasticityNeuronsNeuropathyNociceptionNucleus AccumbensPainPain managementPeripheralPeripheral Nervous SystemPersonsPlayPopulationPre-Clinical ModelProceduresPropertyPsychological reinforcementRoleRunningScienceSignal TransductionSiteSliceSourceSubstance Use DisorderSynapsesTestingTrainingUnited StatesVentral Tegmental AreaWorkbehavior testburden of illnesschronic neuropathic painchronic paincingulate cortexcognitive controlcomorbiditydopaminergic neuronemotion regulationexperienceexperimental studygamma-Aminobutyric Acidhigh rewardhigh riskimprovedin vivoinsightmotivated behaviornerve injuryneuroadaptationneurotransmissionoptogeneticspain behaviorpain processingpain sensitivitypainful neuropathyparabrachial nucleuspostsynapticpresynapticreceptor bindingrelating to nervous systemresponsesham surgeryskillssomatosensoryspared nervesynaptic functiontargeted treatment
项目摘要
PROJECT SUMMARY
Neuropathic pain, a form of chronic pain, is initiated by lesions or disease of the somatosensory nervous system
affects up to 10% of people across the globe. Neuropathic pain results in transsynaptic modifications from the
peripheral nervous system which are propagated to the central nervous system. This CNS plasticity in chronic
pain also underlies the affective and emotional components of chronic pain. Since treatment options for
neuropathic pain are limited and poorly effective, and emotional regulation and cognitive control alters pain
processing, studying affective brain circuity will provide insights into the complex experience of neuropathic pain
and its treatment. The VTA, a nexus of affective and reinforcement learning, is the primary source of
mesocorticolimbic dopamine, and controls the integration of nociceptive cues and pain. VTA dopamine (DA)
neurons generally have reduced firing rates during neuropathic pain, and driving VTA DA neurons during pain
results in analgesia. This highlights the VTA as a potential target for therapeutics for neuropathic pain. However,
the mechanisms underlying this reduction in firing rate are understudied. This proposal will address this
knowledge gap by examining VTA neurons and their synapses following a model of chronic neuropathic pain:
spared nerve injury (SNI). In Aim 1 I will assess DA cell function using ex vivo slice electrophysiology to record
from labelled neurons in mice following SNI or sham surgery, testing the hypothesis that neuropathic injury
reduces intrinsic excitability or depresses excitatory synapses on VTA DA neurons. In Aim 2 I will assess GABA
cell function following, testing the hypothesis that neuropathic injury increases intrinsic excitability or potentiates
excitatory synapses on VTA GABA neurons. Then in Aim 3, I will examine circuit-specific contributions to
plasticity and pain behaviors using a combination of in vivo optogenetics and ex vivo slice electrophysiology.
Together, these studies will increase our understanding of neural underpinnings of neuropathic pain. A greater
understanding of the supraspinal mechanisms of neuropathic pain-induced neuroplasticity will lead to more
targeted therapies in the complex issue of chronic pain. Performing these experiments will allow me to gain
technical and subject matter expertise under the tutelage of an outstanding VTA electrophysiologist: Dr. Kauer.
Her training, in combination with the professional development trainings outlined in this submission, will improve
my ability to communicate my science, increase my scientific rigor through enhanced analytical skills, and
develop my leadership skills. Together these experiments and activities will prepare me to run my own successful
independent research laboratory.
项目总结
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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Claire Manning其他文献
Claire Manning的其他文献
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{{ truncateString('Claire Manning', 18)}}的其他基金
Excitatory neurotransmission in the ventral tegmental area following neuropathic injury
神经性损伤后腹侧被盖区的兴奋性神经传递
- 批准号:
10285423 - 财政年份:2021
- 资助金额:
$ 4.07万 - 项目类别:
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