Astrocytic Contributions to Long Term Memory & Synaptic Plasticity
星形胶质细胞对长期记忆的贡献
基本信息
- 批准号:8267253
- 负责人:
- 金额:$ 3.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-11-16 至 2014-11-15
- 项目状态:已结题
- 来源:
- 关键词:AIDS Dementia ComplexAdrenergic AgentsAdrenergic AntagonistsAdrenergic ReceptorAffectAlzheimer&aposs DiseaseArousalAstrocytesBehavioralBinding ProteinsBrainBrain DiseasesCell Culture TechniquesCellsComplementCouplingD-arabitolDataDendritesDevelopmentDiseaseEngineeringFrequenciesGlial Fibrillary Acidic ProteinGlycogenGlycogen PhosphorylaseHippocampus (Brain)Injection of therapeutic agentIntermediate Filament ProteinsLaboratoriesLactate TransporterLateralLearningLiteratureLong-Term PotentiationMaintenanceMeasuresMediatingMemoryMemory impairmentMetabolicMolecular TargetNeurodegenerative DisordersNeurogliaNeuronsNorepinephrinePathway interactionsPeptide Elongation Factor 1PhasePlayPreparationProcessPropranololProtein BiosynthesisProteinsRattusReportingResearch DesignResistanceRoleSmall Interfering RNASpecificitySynapsesSynaptic plasticityTestingTherapeutic InterventionTimeTrainingWestern BlottingWorkadrenergicanalogbasebehavior testcognitive functionconditioned fearemotional experienceexperienceexpression vectorglycogenolysisin vivoinhibitor/antagonistknock-downlocus ceruleus structurelong term memorynoradrenergicpublic health relevancetool
项目摘要
DESCRIPTION (provided by applicant): Memory consolidation is the process by which the newly learned information, which exists in a labile state, becomes a long-lasting memory that is resistant to disruption2,3,4. Long-term memory consolidation requires de novo protein synthesis, and it is very likely that dendritic protein synthesis is also involved in this process5. Long-term potentiation (LTP) is a persistent increase in synaptic strength, and is considered a cellular correlate for long-term memory8. Like memory consolidation, late forms of LTP (L-LTP) also require protein synthesis, and have been shown to specifically require dendritic protein synthesis as well as somatic protein synthesis9. Memories of emotional experiences such as those produced in the fear conditioning-based inhibitory avoidance (IA) paradigm, are subject to modulation by various hormones35. Noradrenaline is released from the locus coeruleus during arousal and enhances memory via ¿-adrenergic receptors41. The same is true in regards to LTP, which is likewise modulated by noradrenaline10,50. Recent evidence from our laboratory and others suggest that astrocytes play a larger role in both learning and memory and LTP than previously thought. By contributing lactate to neurons through glycogenolysis and transfer via monocarboxylate transporters, astrocytes are critical to memory consolidation and LTP maintenance (see preliminary data). Interestingly, ¿-adrenergic receptors are present on astrocytes and have also metabolic effects in astrocytes when stimulated15,16,37,38,39,40. This project will test the contribution of astrocytes to long-term memory and LTP. Specifically, it will test the hypothesis that astrocytes critically contribute to memory formation by providing astrocytic-neuronal coupling through lactate that supports the high-energy demands associated with activation of dendritic protein synthesis. Furthermore, it will test the hypothesis that the noradrenergic-dependent modulation of memory is mediated by the astrocytic-neuronal coupling.
PUBLIC HEALTH RELEVANCE: The contribution of astrocytes to brain diseases is vast and still very underexplored, but astrocytic and microglial activation has been reported in several neurodegenerative disorders, including AIDS dementia complex, Alzheimer's disease and amyotrophic lateral sclerosis66. This transition may be accompanied by functional deregulation and even degeneration of the astrocytes with the consequent disruption of the crosstalk normally occurring between these cells and neurons67. Thus, incorrect neuron-astrocyte interactions may be involved in neuronal derangement and contribute to disease development, and elucidating the mechanisms that underlie the astrocyte-neuronal coupling in cognitive functions including learning and memory should enable us to better understand normal brain function and identify potential molecular targets for therapeutic intervention in several disorders.
描述(由申请人提供):记忆巩固是一个过程,通过这个过程,新学到的信息,它存在于一个不稳定的状态,成为一个持久的记忆,是抗破坏2,3,4。长期记忆巩固需要从头蛋白质合成,并且很可能树突状蛋白质合成也参与了这一过程5。长时程增强(LTP)是突触强度的持续增加,被认为是长期记忆的细胞相关性8。与记忆巩固一样,LTP的晚期形式(L-LTP)也需要蛋白质合成,并且已被证明特别需要树突蛋白质合成以及体细胞蛋白质合成9。情绪体验的记忆,如在基于恐惧条件反射的抑制性回避(IA)范式中产生的记忆,受到各种情绪的调节35。去甲肾上腺素在觉醒时从蓝斑释放,并通过肾上腺素能受体增强记忆41。LTP也是如此,它同样受到去甲肾上腺素的调节10,50。我们实验室和其他实验室的最新证据表明,星形胶质细胞在学习和记忆以及LTP中发挥的作用比以前认为的要大。星形胶质细胞通过糖原分解和单羧酸转运蛋白转移乳酸到神经元,对记忆巩固和LTP维持至关重要(见初步数据)。有趣的是,â-肾上腺素能受体存在于星形胶质细胞上,并且在受到刺激时也对星形胶质细胞产生代谢影响15,16,37,38,39,40。该项目将测试星形胶质细胞对长期记忆和LTP的贡献。具体来说,它将测试的假设,星形胶质细胞通过提供星形胶质细胞-神经元耦合,通过乳酸支持与树突状蛋白合成的激活相关的高能量需求,关键有助于记忆的形成。此外,它将测试的假设,去甲肾上腺素依赖性调节记忆是由星形胶质细胞神经元耦合介导的。
公共卫生相关性:星形胶质细胞对脑疾病的贡献是巨大的,并且仍然非常未被探索,但是星形胶质细胞和小胶质细胞活化已经在几种神经退行性疾病中被报道,包括AIDS痴呆综合征、阿尔茨海默病和肌萎缩性侧索硬化症66。这种转变可能伴随着功能失调,甚至星形胶质细胞的变性,从而破坏了这些细胞和神经元之间正常发生的串扰67。因此,不正确的神经元-星形胶质细胞相互作用可能参与神经元紊乱,并有助于疾病的发展,阐明认知功能(包括学习和记忆)中星形胶质细胞-神经元偶联的机制,应使我们能够更好地了解正常的脑功能,并确定潜在的分子靶点,用于治疗干预几种疾病。
项目成果
期刊论文数量(0)
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Sarah Stern其他文献
Sarah Stern的其他文献
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{{ truncateString('Sarah Stern', 18)}}的其他基金
Identifying neurons for interoception using simultaneous profiling of activity- and projection- specific populations
使用活动和投射特定群体的同步分析来识别用于内感受的神经元
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10687590 - 财政年份:2023
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Neural circuit mechanisms controlling non-homeostatic feeding
控制非稳态进食的神经回路机制
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$ 3.42万 - 项目类别:
Neural circuit mechanisms controlling non-homeostatic feeding
控制非稳态进食的神经回路机制
- 批准号:
9891700 - 财政年份:2020
- 资助金额:
$ 3.42万 - 项目类别:
Neural circuit mechanisms controlling non-homeostatic feeding
控制非稳态进食的神经回路机制
- 批准号:
10545728 - 财政年份:2020
- 资助金额:
$ 3.42万 - 项目类别:
Neural circuit mechanisms controlling non-homeostatic feeding
控制非稳态进食的神经回路机制
- 批准号:
10297901 - 财政年份:2020
- 资助金额:
$ 3.42万 - 项目类别:
Neural circuit mechanisms controlling non-homeostatic feeding
控制非稳态进食的神经回路机制
- 批准号:
10429408 - 财政年份:2020
- 资助金额:
$ 3.42万 - 项目类别:
Neural circuit mechanisms controlling non-homeostatic feeding
控制非稳态进食的神经回路机制
- 批准号:
10532559 - 财政年份:2020
- 资助金额:
$ 3.42万 - 项目类别:
Astrocytic Contributions to Long Term Memory & Synaptic Plasticity
星形胶质细胞对长期记忆的贡献
- 批准号:
8579807 - 财政年份:2010
- 资助金额:
$ 3.42万 - 项目类别:
Astrocytic Contributions to Long Term Memory & Synaptic Plasticity
星形胶质细胞对长期记忆的贡献
- 批准号:
8402406 - 财政年份:2010
- 资助金额:
$ 3.42万 - 项目类别:
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