Defining Astrocyte Engram Ensembles During Memory Formation
定义记忆形成过程中的星形胶质细胞印迹整体
基本信息
- 批准号:10722056
- 负责人:
- 金额:$ 44万
- 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:2023-08-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAblationAcuteAlzheimer&aposs DiseaseAmnesiaAnxietyAstrocytesBehaviorBehavioralBrainCalciumCell SeparationCellsClozapineCognitionDataDementiaDiphtheria ToxinDiseaseEventExhibitsExperimental DesignsExposure toFOS geneFreezingGene ExpressionGoalsHippocampusImageImmediate-Early GenesImpairmentLabelLearningLigandsMapsMeasuresMemoryMemory impairmentMolecularMolecular AnalysisMorphologyMusNatureNeuronsOutputOxidesPhysiologicalPlayPopulationPost-Traumatic Stress DisordersProcessPropertyResolutionRetrievalRoleSignal TransductionSliceSpecificitySynapsesSynaptic plasticitySystemTestingTraumaViralViruscalcium indicatorconditioned feardentate gyrusexperimental studyinducible gene expressioninsightmemory encodingmemory processmemory recallmemory retrievalnervous system disorderneuronal circuitryprospectivereconstructiontooltranscriptome sequencingtwo-photon
项目摘要
Summary
Astrocytes play diverse and indispensable roles in brain function. Participating as a component of the ‘tripartite
synapse’, a single astrocyte is estimated to contact up to 100,000 neuronal synapses in the hippocampus. Notably,
studies have identified essential functions of astrocytes in hippocampal circuits, where astrocytes are required for
regulating synaptic plasticity including LTP, a key process associated with learning and memory. Recent studies
have shown that enhancing Gq-signaling in astrocytes promotes LTP and enhances acute memory, while impairing
astrocyte function suppresses LTP and memory, highlighting central roles for astrocytes in memory-dependent
tasks. Learning events invoke activity and plasticity among a discrete ensemble of cells. Activation of these
ensembles by learning and reactivated during memory recall constitute the physical substrate of memory and are
referred to as engrams. Despite the critical involvement of astrocytes in learning and memory processes, the study
of memory engrams has been limited exclusively to neuronal ensembles. The goal of this proposal is to study the
potential of astrocyte engrams as a substrate of memory and to understand the nature and function of hippocampal
astrocyte ensembles.
We have created a host of mouse lines and associated AAV-viral tools the enable us to label and
manipulate astrocytes during learning events in the hippocampus. Preliminary studies with these tools indicate that
we can label ensembles of astrocytes after learning and that reactivation of these same astrocytes promotes
memory recall. Based on the strength of these preliminary data and the associated tools we have built, we propose
the following specific aims. In specific aim1, we will label astrocyte ensembles after learning and characterize
whether they exhibit engram properties. In specific aim2, we will manipulate the prospective engram astrocyte
populations and determine whether they encode memory storage and recall. In specific aim3, we will characterize
the cellular and molecular properties of these labeled astrocyte engram populations.
概括
星形胶质细胞在大脑功能中发挥着多样化且不可或缺的作用。作为“三方”的组成部分参与
突触”中,单个星形胶质细胞估计可接触海马体中多达 100,000 个神经元突触。尤其,
研究已经确定了星形胶质细胞在海马回路中的基本功能,其中星形胶质细胞需要
调节突触可塑性,包括 LTP,这是与学习和记忆相关的关键过程。最近的研究
研究表明,增强星形胶质细胞中的 Gq 信号传导可促进 LTP 并增强急性记忆,同时损害
星形胶质细胞功能抑制 LTP 和记忆,凸显星形胶质细胞在记忆依赖中的核心作用
任务。学习事件会激发离散细胞群的活动和可塑性。激活这些
通过学习并在记忆回忆过程中重新激活的整体构成了记忆的物理基础,并且是
称为印迹。尽管星形胶质细胞在学习和记忆过程中发挥着重要作用,但该研究
记忆印迹的研究仅限于神经元群。本提案的目标是研究
星形胶质细胞印迹作为记忆基质的潜力并了解海马的性质和功能
星形胶质细胞群。
我们已经创建了许多小鼠品系和相关的 AAV 病毒工具,使我们能够标记和
在海马体的学习活动期间操纵星形胶质细胞。使用这些工具的初步研究表明
我们可以在学习后标记星形胶质细胞群,并且这些相同星形胶质细胞的重新激活会促进
记忆回忆。根据这些初步数据的强度和我们构建的相关工具,我们建议
具体目标如下。在具体目标1中,我们将在学习后标记星形胶质细胞集合并表征
它们是否表现出印迹特性。在具体目标2中,我们将操纵预期的印迹星形胶质细胞
群体并确定它们是否编码记忆存储和回忆。在具体的目标3中,我们将描述
这些标记的星形胶质细胞印迹群的细胞和分子特性。
项目成果
期刊论文数量(0)
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Benjamin Deneen其他文献
Benjamin Deneen的其他文献
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{{ truncateString('Benjamin Deneen', 18)}}的其他基金
Astrocyte Transcriptional Dependencies in Brain Circuits
脑回路中星形胶质细胞的转录依赖性
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10665221 - 财政年份:2023
- 资助金额:
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Systematic Characterization and Targeting of Neomorphic Drivers in Cancer
癌症新形态驱动因素的系统表征和靶向
- 批准号:
10717973 - 财政年份:2023
- 资助金额:
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Transcriptional Regulation in ZFTA-RELA Ependymoma
ZFTA-RELA 室管膜瘤的转录调控
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10736436 - 财政年份:2023
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Cellular and Molecular Mechanisms of GBM Infiltration
GBM 浸润的细胞和分子机制
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10583559 - 财政年份:2022
- 资助金额:
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Cellular and Molecular Mechanisms of GBM Infiltration
GBM 浸润的细胞和分子机制
- 批准号:
10383061 - 财政年份:2022
- 资助金额:
$ 44万 - 项目类别:
MOLECULAR AND CELLULAR CONTROL OF INJURY-INDUCED ASTROGENESIS
损伤引起的星形细胞生成的分子和细胞控制
- 批准号:
10335708 - 财政年份:2021
- 资助金额:
$ 44万 - 项目类别:
Defining Roles for Astrocyte Subpopulations in the Aging Brain
定义星形胶质细胞亚群在衰老大脑中的作用
- 批准号:
10192033 - 财政年份:2021
- 资助金额:
$ 44万 - 项目类别:
Defining Roles for Astrocyte Subpopulations in the Aging Brain
定义星形胶质细胞亚群在衰老大脑中的作用
- 批准号:
10581539 - 财政年份:2021
- 资助金额:
$ 44万 - 项目类别:
Defining Roles for Astrocyte Subpopulations in the Aging Brain
定义星形胶质细胞亚群在衰老大脑中的作用
- 批准号:
10390425 - 财政年份:2021
- 资助金额:
$ 44万 - 项目类别:
Defining Roles for Astrocyte Subpopulations in the Aging Brain
定义星形胶质细胞亚群在衰老大脑中的作用
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10708356 - 财政年份:2021
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