The Impact of Individual Vulnerability to Stress on Alcohol and Drug Seeking
个人对压力的脆弱性对酗酒和吸毒的影响
基本信息
- 批准号:10755029
- 负责人:
- 金额:$ 3.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAlcoholsAmygdaloid structureAnimalsAssociation LearningBasic ScienceBiologicalBrainCalciumCellsCharacteristicsCodeCoupledCuesData AnalysesDesire for foodDevelopmentDiagnosisDiseaseDrug usageEmotionalEventExhibitsExposure toExtinctionFOS geneFellowshipFemaleFrightFunctional disorderGeneticGoalsHandednessHeavy DrinkingHeterogeneityHumanImageInbred MouseIndividualLearningLeftMaintenanceMeasuresMediatingMemoryMental disordersMilitary PersonnelModelingMolecularMusNegative ValenceNeurobiologyNeuronsOutputPerformancePersonsPharmaceutical PreparationsPhasePhenotypePhotonsPopulationPositive ValencePost-Traumatic Stress DisordersPostdoctoral FellowPredispositionPrevalenceProtocols documentationPublic HealthResearchResistanceRiskRodentStressStructureStudy modelsSubstance Use DisorderSymptomsSynapsesSystemTechniquesTestingTherapeuticTissue-Specific Gene ExpressionTrainingTraumaVulnerable PopulationsWomanWorkacute stressalcohol use disordercomorbidityconditioningdeep sequencingdrug of abuseexperiencefear memoryimmunoreactivityimprovedin vivoin vivo calcium imagingin vivo imaginginsightmalemembermemory recallneuralneurophysiologyoptogeneticsrecruitresilienceresilience factorrestraintrestraint stresssexstress disorderstress resiliencestressortranscriptomicstraumatic event
项目摘要
PROJECT SUMMARY
Stress leads to the enhancement of memory in both humans and animals. This stress-enhanced memory has
relevance to stress-related psychiatric disorders, such as posttraumatic stress disorder (PTSD), which is marked
by heightened, perseverant memories of trauma. Interestingly, only approximately 10-20% of people develop
the enduring symptoms of PTSD, despite nearly everyone experiencing at least one traumatic event in their
lifetime. In addition, rates of PTSD are higher among women and military personnel. A protocol was developed
by this group that results in differential susceptibility to stress enhancement of a remote (one month old) fear
memory among male mice and a greater propensity for enhancement in females. Despite the clear importance
of understanding the mechanisms supporting long-lasting, perseverant memory, the majority of basic memory
research focuses on recent (~ 1 day old), not remote memory and does not incorporate a stress component.
Additional research performed by the group with this protocol identified the basolateral amygdala (BLA) has a
critical hub mediating stress-enhanced fear memory and the associated differential susceptibility. The primary
goal of the current application is to delineate how stress engages and alters the function of the BLA to drive
differential susceptibility to stress-enhanced fear memory. The work will place particular focus on sex as a
biological variable and lateralized function of the BLA. Regarding the latter, the right hemisphere BLA is
associated with negative valence, while the left is associated with positive valence. This is conserved from
humans to rodents but is understudied in basic research. The central hypothesis of this proposal is that stress
leads to lasting impacts on the BLA, resulting in differential susceptibility to remote stress-enhanced fear
memory. The working hypothesis to be explored is that an intense acute stressor alters subsequent fear memory
strength by influencing the recruitment of specific BLA cell populations to the memory trace. Work leading up to
this proposal (F99 Aim 1A) details studies characterizing identity and laterality of neural ensembles supporting
stress-induced memory enhancement. To examine how stress impacts experience coding to influence stress-
enhanced fear memory (F99 Aim 1B), I will train in execution and data analysis of in vivo calcium imaging of the
BLA. In transitioning to a postdoctoral fellowship, I will focus on research based on the high rate of co-morbidity
between stress disorders and alcohol and substance sue disorders (K00). The research will incorporate
neurophysiological and deep sequencing measures to further study how stress individually impacts function of
the BLA and associated circuitry to influence alcohol or drug seeking. The proposed work will provide a much-
needed, deep characterization of the impact of stress on the brain in the context of differential stress
susceptibility. This information will then be used to guide cellular, molecular and circuit level mechanistic studies,
with the goal of identifying therapeutic strategies.
项目摘要
压力导致人类和动物记忆力的增强。这种压力增强的记忆
与压力相关的精神障碍,如创伤后应激障碍(PTSD),这是显着的相关性
对创伤的强烈而持久的记忆有趣的是,只有大约10-20%的人会发展成
PTSD的持久症状,尽管几乎每个人都经历过至少一次创伤事件,
辈子此外,女性和军人的PTSD发病率更高。制定了一项协议,
这一组的结果是不同的敏感性,以加强压力的远程(一个月大)恐惧
雄性小鼠的记忆力增强,雌性小鼠的记忆力增强倾向更大。尽管很明显
理解支持持久、持久记忆的机制,大部分基本记忆
研究集中在最近(约1天),而不是远程记忆,并没有纳入压力组件。
该研究小组使用该方案进行的其他研究表明,基底外侧杏仁核(BLA)具有
关键枢纽介导的压力增强恐惧记忆和相关的差异易感性。主
本申请的目的是描述压力如何参与和改变BLA的功能,以驱动
对压力的敏感性差异增强了恐惧记忆。这项工作将特别关注性,
BLA的生物学变量和偏侧功能。关于后者,右半球BLA是
与负效价相关,而左与正效价相关。这是保守的,
从人类到啮齿动物,但在基础研究中研究不足。该提议的中心假设是压力
导致对BLA的持久影响,导致对远程压力增强的恐惧的不同易感性
记忆有待探讨的工作假设是,一个强烈的急性应激改变了随后的恐惧记忆
通过影响特定BLA细胞群向记忆痕迹的募集来增强记忆力。工作导致
这一提议(F99 Aim 1A)详细描述了表征神经系综的同一性和偏侧性的研究,
压力导致的记忆增强为了研究压力如何影响体验编码来影响压力-
增强恐惧记忆(F99 Aim 1B),我将训练在体内钙成像的执行和数据分析,
BLA.在过渡到博士后研究期间,我将专注于基于高共病率的研究
酒精和物质性精神障碍(K 00)之间的关系。研究将结合
神经生理学和深度测序措施,以进一步研究压力如何单独影响功能,
BLA和相关电路影响酒精或药物寻求。这项工作将提供一个非常-
需要深入描述差异压力背景下压力对大脑的影响
易感性这些信息将用于指导细胞,分子和电路水平的机制研究,
目的是确定治疗策略。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Jose Colom Lapetina的其他文献
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