Linking Neuron-Astrocyte Communication to Long-Term Changes in Neural Circuit Function and Behavior
Linking Neuron-Astrocyte Communication to Long-Term Changes in Neural Circuit Function and Behavior
批准号:
10294805
负责人:
Cagla Eroglu
金额:
$43.4万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-08-15 至 2026-07-31
关键词:
AffectAstrocytesBehaviorBehavioralBrainCRISPR/Cas technologyCell AdhesionChemosensitizationChromatinCollaborationsCommunicationComplementComplexCuesDataDevelopmentERG geneEpigenetic ProcessEquilibriumExcitatory SynapseFutureGene ExpressionGeneticGiant CellsGoalsImageImmediate-Early GenesImpairmentIndividualInfiltrationInhibitory SynapseInstinctInstructionLearningLinkMeasuresMediatingMemoryModalityMolecularMorphologyMusNeurogliaNeuronsNeuropilNeurotransmittersNew AcceptorsOutcomePathway interactionsPerformancePlayPrefrontal CortexPropertyProteomicsReporter GenesRewardsRoleSensorySignal PathwaySignal TransductionStructureSumSupporting CellSynapsesSynaptic TransmissionTestingTimeTrainingTransgenic MiceViralawakebasebehavior changecholinergicdetectorepigenomeexperienceextracellularhistone modificationin vivolearned behaviormolecular modelingmultiphoton imagingneural circuitneuronal circuitryneuroregulationnoradrenergicnovelsynaptic functionsynaptogenesistooltransmission process
中文摘要
项目概要:项目3-将神经元-星形胶质细胞通信与长期
神经回路功能和行为的变化
星形胶质细胞,通常被称为被动支持细胞,实际上与大量的
神经元突触和感觉他们的活动,使他们成为理想的细胞探测器和集成商,
突触传递此外,星形胶质细胞重塑突触回路,并通过指示突触
形成和可塑性。然而,星形胶质细胞是否以及如何在介导
复杂的行为仍然未知。
在这个合作项目中要测试的首要假设是,星形胶质细胞作为时间
整合子,其检测并整合局部突触活动和长投射神经调节
传动.在这个子项目(项目3)中,要检验的具体假设是,
星形胶质细胞个体或合胞体的整合特性允许它们被
在获得目标导向的行为过程中经验驱动的突触活动。这些夹带的星形胶质细胞
通过星形胶质细胞染色质的表观遗传重塑与学习行为"接合",导致
星形胶质细胞基因表达、结构和功能的长期变化(Aim 1)。这种接合
允许星形胶质细胞以两种方式重新连接局部突触电路:1)通过改变
兴奋性和/或抑制性突触,从而调节局部兴奋/抑制
平衡,和2)通过改变它们的突触关联和神经元浸润,从而控制
神经递质的细胞外浓度。初步发现表明星形胶质细胞-
介导的突触重塑不是学习所必需的,而是为了适应性。
学习行为。这些发现指出了这些拟议的行为参与的具体作用,
星形胶质细胞在重新布线的基础电路,以准备这些电路为未来的可能性,
学习的行为不再有效-例如,实现预期结果的努力超过了
奖励的价值(Aim2)。这些行为参与的星形胶质细胞与它们的
神经元对应部分,这两者都可以通过立即早期基因表达来鉴定。期间
行为的表现,这些星形胶质细胞-神经元集合体被准备好感知行为的变化。
结果偶然性,以便他们可以指示停止学习的行为(目标3)。
与其他团队合作,这些假设将在三个目标和一个机械蓝图中进行测试。
用于清醒行为小鼠大脑中星形胶质细胞-神经元通信的信号将被产生。因此,我们认为,
这些拟议的研究准备揭示星形胶质细胞如何响应,整合和调节
神经元的连接性。此外,与其他团队一起,这些发现
将指导新的遗传编码指标和病毒工具的开发,以询问神经元,
神经胶质细胞回路在体内(项目2和4)和通知,测试,并完善预测神经元-
星形胶质细胞信号传导机制的感觉运动处理(项目1)。
英文摘要
Project Summary: Project 3- Linking Neuron-Astrocyte Communication to Long-Term
Changes in Neural Circuit Function and Behavior
Astrocytes, which are often dubbed as the passive support cells, in fact closely associate with a vast number
of neuronal synapses and sense their activity, making them ideal cellular detectors and integrators of
synaptic transmission. Moreover, astrocytes remodel synaptic circuitry and function by instructing synapse
formation and plasticity. However, whether and how astrocytes play an instructive role to mediate
complex behaviors remains unknown.
The overarching hypothesis to be tested in this collaborative project is that astrocytes act as temporal
integrators, which detect and integrate local synaptic activity and long-projecting neuromodulatory
transmissions. In this subproject (Project 3), the specific hypothesis to be tested is that signal
integration property of individual or syncytia of astrocytes allows them to become entrained by
experience-driven synaptic activity during acquisition of goal-directed behaviors. These entrained astrocytes
become “engaged” with the learned behavior by epigenetic remodeling of astrocytic chromatin, leading to
long-term changes in astrocytic gene expression, structure and function (Aim1). This engagement
allows the astrocytes to rewire the local synaptic circuitry in two ways; 1) by changing the numbers of
excitatory and/or inhibitory synapses within their domains, thus modulate the local excitation/inhibition
balance, and 2) by altering their synapse association and neuropil infiltration, thus controlling
extracellular concentrations of neurotransmitters. Preliminary findings suggest that astrocyte-
mediated synaptic remodeling is not necessary for learning, but rather for the adaptability of the
learned behaviors. These findings point out a specific role for these proposed behaviorally-engaged
astrocytes in rewiring of the underlying circuits to prepare these circuits for a future eventuality, in
which the learned behavior is no longer effective -e.g. the effort to achieve the desired outcome exceeds
the value of the reward (Aim2). These behaviorally-engaged astrocytes form ensembles with their
neuronal counter parts, both of which can be identified by immediate early gene expression. During the
performance of behaviors, these astrocyte-neuron ensembles are primed to sense the changes in action/
outcome contingency so that they can instruct to stop the learned behaviors (Aim3).
Working in concert with other teams, these hypotheses will be tested in three aims, and a mechanistic blueprint
for astrocyte-neuron communication in the awake behaving mouse brain will be generated. Therefore,
these proposed studies are poised to reveal how astrocytes respond to, integrate, and modulate
neuronal connectivity in long-time scales. Furthermore, in conjunction with other teams, these findings
will guide the development of novel genetically encoded indicators and viral tools to interrogate neuron-
glia circuits in vivo (Projects 2 and 4) and inform, test, and refine predictions for neuron-
astrocyte signaling mechanisms underlying sensorimotor processing (Project 1).
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Astrocyte Modulation of Neural Circuit Function and Behavior
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批准号:10294800
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项目类别:
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资助金额:$223.26万
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财政年份:2021
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负责人:Cagla Eroglu
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依托单位:
Astrocyte Modulation of Neural Circuit Function and Behavior
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批准号:10461222
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依托单位:
Linking Neuron-Astrocyte Communication to Long-Term Changes in Neural Circuit Function and Behavior
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项目类别:
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依托单位:
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批准号:10693174
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项目类别:
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负责人:Cagla Eroglu
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Control of Astrocyte Development and Astrocyte-Synapse Interactions
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批准号:9930268
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项目类别:
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资助金额:$4.5万
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财政年份:2019
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依托单位:
Control of Astrocyte Development and Astrocyte-Synapse Interactions
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批准号:9900048
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项目类别:
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资助金额:$42.29万
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财政年份:2018
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负责人:Cagla Eroglu
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依托单位:
Control of Astrocyte Development and Astrocyte-Synapse Interactions
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批准号:10376297
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项目类别:
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资助金额:$34.52万
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财政年份:2018
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负责人:Cagla Eroglu
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依托单位:
New Proteomic and Genome Engineering Approaches to Decipher Astrocyte Function at Synapses
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批准号:9789247
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项目类别:
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资助金额:$70.53万
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财政年份:2018
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负责人:Cagla Eroglu
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依托单位:
The Regulation of Synaptic Connectivity and Homeostasis by Huntingtin
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批准号:9083719
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项目类别:
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资助金额:$34.25万
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财政年份:2016
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负责人:Cagla Eroglu
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依托单位:
Control of synapse formation and maturation by astrocytes
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批准号:8373445
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项目类别:
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资助金额:$34.81万
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财政年份:2012
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负责人:Cagla Eroglu
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依托单位:
Control of synapse formation and maturation by astrocytes
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批准号:8475573
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项目类别:
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资助金额:$33.42万
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财政年份:2012
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负责人:Cagla Eroglu
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依托单位:
Control of synapse formation and maturation by astrocytes
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批准号:8654325
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项目类别:
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资助金额:$34.81万
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财政年份:2012
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负责人:Cagla Eroglu
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依托单位:
国内基金
海外基金
Ascl1介导Wnt/beta-catenin通路在TLE海马硬化中反应性Astrocytes异常增生的作用及调控机制
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批准号:31760279
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项目类别:地区科学基金项目
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资助金额:35.0万元
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批准年份:2017
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负责人:丁银秀
-
依托单位: