The role of protein kinase Mzeta in hippocampal-dependent memory maintenance.
蛋白激酶 Mzeta 在海马依赖性记忆维持中的作用。
基本信息
- 批准号:8209722
- 负责人:
- 金额:$ 4.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-01-01 至 2013-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAmygdaloid structureAnimalsBilateralBiologicalBrainCannulasCatalytic DomainComplexConditioned StimulusCuesDorsalElementsEpisodic memoryFrightGoalsHippocampus (Brain)HumanInjection of therapeutic agentKnowledgeLearningLiteratureLong-Term PotentiationMaintenanceMemoryMemory DisordersMicroinjectionsMolecularPatientsPeptidesPharmaceutical PreparationsPhasePhysiologicalPlayProcessProtein IsoformsProtein KinaseProtein Kinase CProtein Kinase InhibitorsRadialRattusResearchRewardsRoleStimulusStructureSucroseSynapsesTaste PerceptionTestingTimeTrainingTranslatingWorkanalogarmbaseconditioned fearconditioningimprovedinhibitor/antagonistlong term memorypreventprocedural memoryprotein kinase inhibitorpublic health relevancerelational memoryresearch studytherapy developmentway finding
项目摘要
DESCRIPTION (provided by applicant): The broad goal of the proposed project is to understand how long-term memories are stored in the brain through the activity of protein kinase Mzeta (PKM?). Using rats, this project will determine the specific subset of hippocampal-dependent associations that require PKM? activity for maintenance to better understand PKM? requirements in the brain. Three specific aims will be addressed. The first aim is to determine whether PKM? activity is differentially required in the hippocampus and amygdala to maintain aversive, contextually-based memories. To achieve this aim, trace fear conditioning (TFC) will be used to create an aversive context-based memory that requires both the hippocampus and amygdala for acquisition (1,2). In TFC, a neutral conditioned stimulus (CS) is paired with an aversive unconditioned stimulus (US) with an empty trace period separating the two stimuli. The second aim, which addresses whether appetitive spatial memory requires hippocampal PKM? activity, will be achieved using the spatially-based 8-arm radial arm maze task. In the radial arm maze task, rats must use spatial cues to determine which 4 of the 8 available arms contain hidden sucrose pellets. This task requires the hippocampus for acquisition and relies on external spatial cues in the training room, rather than contextual cues present within the apparatus (3). The final aim is to determine whether different requirements exist for hippocampal PKM? activity in the maintenance of spatial and contextual appetitive memory associations. To achieve this goal, the place conditioning task will be used to create a hippocampal- dependent appetitive context memory that can be directly compared with the spatial radial arm maze memory used in aim 2. In place conditioning, sucrose pellets are repeatedly available in one context while no reward is provided in a second context, leading the animal to prefer the sucrose-paired context in a subsequent test (40). In order to test the requirement for hippocampal PKM? activity in each of these forms of memory, a specific, potent inhibitor of PKM? activity called ?-pseudosubstrate inhibitory peptide (ZIP) will be locally microinjected into the dorsal hippocampus or amygdala during the storage phase of each memory (5). Animals will be prepared with bilateral cannulae aimed at the appropriate structure to allow for restricted, local injection of the drug. This set of experiments will elucidate whether PKM? is required to maintain a broad set of hippocampal- dependent memories or whether it only maintains an exclusive subset of memories that require the hippocampus for acquisition. This research has important implications for both improving memory storage and disrupting maladaptive memory storage in human patients.
PUBLIC HEALTH RELEVANCE: This project will expand the current literature on the physiological underpinnings of long-term memory storage. Enhanced understanding of the biological mechanisms underlying memory maintenance is necessary not only to increase our basic knowledge of this process, but also to potentially translate research findings to both normal and disordered memory in humans.
描述(由申请人提供):该项目的主要目标是了解长期记忆是如何通过蛋白激酶Mzeta(PKM?)的活性储存在大脑中的。利用大鼠,该项目将确定需要PKM?的海马区依赖关联的特定子集。维护活动以更好地了解PKM?大脑中的需求。将解决三个具体目标。第一个目标是确定PKM?海马体和杏仁核需要不同的活动来维持厌恶的、基于背景的记忆。为了实现这一目标,痕迹恐惧条件反射(TFC)将被用来创造一种基于背景的厌恶记忆,这需要海马体和杏仁核来获取(1,2)。在TFC中,中性条件刺激(CS)与厌恶的无条件刺激(US)配对,两个刺激之间有一个空的踪迹周期。第二个目标是,食欲空间记忆是否需要海马区PKM?活动,将使用基于空间的8臂径向臂迷宫任务实现。在放射状手臂迷宫任务中,大鼠必须使用空间线索来确定8只可用手臂中的哪4只含有隐藏的蔗糖丸。这项任务需要海马体进行获取,并依赖于训练室中的外部空间线索,而不是设备中存在的上下文线索(3)。最终目的是确定是否存在对海马区PKM的不同要求?维持空间和语境的食欲记忆联系的活动。为了实现这一目标,地点条件作用任务将被用来创建海马体依赖的食欲背景记忆,该记忆可以直接与目标2中使用的空间放射状手臂迷宫记忆进行比较。在地点条件作用中,蔗糖丸在一个背景下重复可用,而在第二个背景下不提供奖励,导致动物在随后的测试中更喜欢蔗糖配对的背景(40)。为了检测海马区PKM?这些形式的记忆中的每一种都有活性,是一种特定的、有效的PKM抑制因子?在每个记忆的存储阶段,被称为?-伪底物抑制肽(ZIP)的活性将被局部微量注射到背侧海马体或杏仁核(5)。动物将准备针对适当结构的双侧套管,以允许限制性的局部注射药物。这组实验将阐明PKM?是否需要维持广泛的海马体依赖记忆,或者它是否只维持需要海马体进行获取的记忆的一个专有子集。这项研究对改善人类患者的记忆存储和扰乱适应不良的记忆存储都有重要的意义。
与公共健康相关:这个项目将扩展目前关于长期记忆存储的生理基础的文献。加强对记忆维持的生物学机制的理解不仅是增加我们对这一过程的基本知识所必需的,而且还可能将研究结果转化为人类正常和紊乱的记忆。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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JANINE LYNN KWAPIS其他文献
JANINE LYNN KWAPIS的其他文献
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{{ truncateString('JANINE LYNN KWAPIS', 18)}}的其他基金
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10002164 - 财政年份:2019
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Epigenetic regulation of the circadian gene Per1 in age-related memory impairments
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10171743 - 财政年份:2019
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Epigenetic repression of synaptic plasticity and memory in the aging brain
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9198722 - 财政年份:2016
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The role of protein kinase Mzeta in hippocampal-dependent memory maintenance.
蛋白激酶 Mzeta 在海马依赖性记忆维持中的作用。
- 批准号:
8059965 - 财政年份:2011
- 资助金额:
$ 4.22万 - 项目类别:
The role of protein kinase Mzeta in hippocampal-dependent memory maintenance.
蛋白激酶 Mzeta 在海马依赖性记忆维持中的作用。
- 批准号:
8399106 - 财政年份:2011
- 资助金额:
$ 4.22万 - 项目类别: