Vagus nerve stimulation targets fear pathways to enhance extinction of conditioned fear
迷走神经刺激针对恐惧通路以增强条件性恐惧的消除
基本信息
- 批准号:10467846
- 负责人:
- 金额:$ 55.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:AffectAmygdaloid structureAnatomyAnimalsAnxietyAnxiety DisordersAreaArousalAxonBehavioralBrainBypassCervicalCoupledCuesDataDevelopmentDiseaseDropoutEmotionalEpinephrineExhibitsExposure toExtinction (Psychology)FrightGoalsGoldHippocampus (Brain)HumanImpairmentIndividualInfusion proceduresLeadLearningLeftMaintenanceMedialMediatingMemoryMicrodialysisNeuromodulatorNeuronsNorepinephrineParasympathetic Nervous SystemPathway interactionsPatientsPatternPeripheralPersonsPlayPost-Traumatic Stress DisordersPrefrontal CortexProcessPublishingRattusResearchRoleSignal TransductionStimulusSynapsesSynaptic plasticityTestingThinkingTrainingTransgenic OrganismsTraumaTyrosine 3-MonooxygenaseVagus nerve structureWorkbasebehavior testconditioned fearconditioningdesignexperienceexperimental studyfear memoryfightingimprovedinnovationinsightlearning extinctionlocus ceruleus structurememory consolidationneuromechanismneuroregulationnoradrenergicoptogeneticspatient populationpre-clinicalpreventrelating to nervous systemresponsestandard of caresuccesstherapeutic developmenttherapy developmenttraumatic eventvagus nerve stimulation
项目摘要
PROJECT SUMMARY
Emotionally traumatic experiences can lead to maladaptive memories that are enduring and intrusive. The goal
of exposure-based therapies is to extinguish conditioned fears through repeated, unreinforced exposures to
reminders of traumatic events. The extinction of conditioned fear depends upon the consolidation of new
memories made during exposure to reminders. An impairment in extinction recall, observed in certain patient
populations, can interfere with progress in exposure-based therapies, and the drive to avoid thoughts and
reminders of the trauma can undermine compliance and increase dropout rate. Development of an effective
adjunctive therapy would ideally improve the tolerability of therapy and/or improve the consolidation and
maintenance of the extinction memory.
We have recently demonstrated in rats that, compared to exposure alone, exposure paired with vagus nerve
stimulation (VNS) enhances the extinction of fear-based memories. Under stressful conditions, the vagus nerve
responds to elevations in epinephrine and signals the brain to facilitate the storage of new memories while, as
part of the parasympathetic nervous system, it slows the sympathetic “fight-or-flight” response. We propose that
stimulation of the left cervical vagus nerve during exposure to conditioned cues signals the brain to store new
memories just as epinephrine or emotional arousal would do but bypasses the peripheral sympathetic response.
In support of this hypothesis, we have found that VNS accelerates extinction, reverses extinction impairments,
promotes generalization of extinction, and prevents reinstatement of conditioned fear in rats.
VNS is thought to work by increasing the activity of neuromodulators throughout the brain, producing a synaptic
state that is conducive to plasticity. In particular, the locus coruleus (LC) is thought to play a critical role in VNS
efficacy by supplying noradrenergic input directly to multiple regions of the extinction network, including the
prefrontal cortex (PFC), the basolateral amygdala (BLA), and the hippocampus (HIP). Here, we propose
behavioral experiments designed to evaluate whether VNS produces more persistent and generalized extinction
memories, which would provide important preclinical evidence that VNS could be an effective adjunct to
exposure-based therapies. To elucidate the mechanisms by which VNS promotes its effects, we propose to
optogenetically manipulate the LC, and to simultaneously record from PFC, BLA, and HIP during conditioning,
extinction, and post-extinction behavioral testing.
By increasing our understanding of the mechanisms by which VNS enhances extinction of conditioned fear,
these studies will support treatment development for patients, and provide new fundamental insights into
the neuromodulatory mechanisms of LC signaling on extinction-related plasticity.
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)
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Christa McIntyre其他文献
Christa McIntyre的其他文献
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{{ truncateString('Christa McIntyre', 18)}}的其他基金
Vagus nerve stimulation targets fear pathways to enhance extinction of conditioned fear
迷走神经刺激针对恐惧通路以增强条件性恐惧的消除
- 批准号:
10616604 - 财政年份:2022
- 资助金额:
$ 55.56万 - 项目类别:
Vagus nerve stimulation targets fear pathways to enhance extinction of conditioned fear
迷走神经刺激针对恐惧通路以增强条件性恐惧的消除
- 批准号:
10391040 - 财政年份:2021
- 资助金额:
$ 55.56万 - 项目类别:
Mechanisms of Extinction of Conditioned Fear by Vagus Nerve Stimulation
迷走神经刺激消除条件性恐惧的机制
- 批准号:
8580886 - 财政年份:2013
- 资助金额:
$ 55.56万 - 项目类别:














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