Temporal Processing by Growth Factors in Memory Formation
记忆形成中生长因子的时间处理
基本信息
- 批准号:10397503
- 负责人:
- 金额:$ 47.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAfferent NeuronsAnimalsAplysiaAttentionBindingBiologicalBiological ModelsBrainCell NucleusCellsClinicalCognition DisordersCytosolDataDevelopmentDiseaseEventExhibitsExtracellular ProteinExtracellular Signal Regulated KinasesExtracellular SpaceGenetic TranscriptionGoalsGrowth FactorHeartHumanLaboratoriesLearningLigandsMEKsMediatingMemoryMental HealthMitogen-Activated Protein KinasesMolecularNatureNeurodegenerative DisordersNeurosciencesNuclearPathway interactionsPatternPhosphorylationPhosphotransferasesPhysiologic pulseProcessPublishingRegulationResearchRoleSeriesSerotoninShockSignal TransductionSiteSpecificityStimulusSynapsesSynaptic plasticitySystemTestingTherapeutic AgentsTimeTrainingTransforming Growth Factor betaUp-RegulationWorkanalogbasecausal modeldetectorexperimental studyextracellularinhibitorinsightlong term memorymanmemory acquisitionnervous system disordernovelnovel strategiesprogramsresponsetherapeutically effectivetime intervaltraining projectvirtual
项目摘要
PROJECT SUMMARY/ABSTRACT
A growing body of evidence suggests that growth factors (GFs), once considered to function mainly in
development, also regulate synaptic plasticity and memory in the adult. This proposal reflects on an ongoing
research program in our laboratory that has focused on the role of GFs in memory formation. The primary
focus of this current project is to examine GF-mediated memory formation from a novel perspective, which
takes into account the temporal aspect of their activity as part of the cellular computation involved in forming
memories.
Repeated-trial learning, a fundamental form of memory acquisition exhibited by virtually all animals, including
man, requires a temporal interaction between an ongoing stimulus and the delayed effects of a previous
stimulus. We will use a powerful paradigm to study repeated-trial training in the marine mollusk Aplysia, which
develops long-term memory (LTM) for sensitization after only two training trials, but only if they are separated
by a permissive and surprisingly specific time interval of ~45 min. This minimal system clearly separates the
initiating stimulus (Trial 1) from the repeated stimulus (Trial 2), providing unparalleled access to the temporal
interactions underlying repeated-trial LTM. We will investigate two GF-dependent mechanisms that our
preliminary evidence suggests contribute significantly to temporal processing at the heart of repeated-trial
learning. The first (explored in AIM 1) is a distributed mechanism for GF-dependent phosphorylation of
extracellularly regulated kinase (ERK). The second mechanism (explored in AIM 2) is the multi-step signaling
of a specific GF, TGFβ, which we propose similarly integrates the timing of training trials. Finally, in AIM 3 we
will try to establish causal connections between the timing of single ERK phosphorylation, TGFβ availability,
and the persistent effects of two-trial training
The project holds promise for significant impact from both a basic scientific perspective and a clinical
perspective. From a basic scientific perspective, Aplysia provides an exceptional experimental system that has
the potential to demonstrate causal linkages between GF-mediated memory formation and its underlying
synaptic and molecular mechanisms, while simultaneously exploring the temporal features of those
mechanisms. And from a clinical perspective, the impact of this project addresses a major challenge in mental
health: to understand and treat the devastating cognitive disorders that accompany neurodegenerative
diseases. GF signaling has been directly implicated in many of these diseases and, since GFs are extracellular
proteins, understanding when and where they act in the brain during memory formation could provide novel
strategies for developing more specific and more effective therapeutic agents.
项目总结/文摘
项目成果
期刊论文数量(0)
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Thomas J Carew其他文献
Thomas J Carew的其他文献
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{{ truncateString('Thomas J Carew', 18)}}的其他基金
Temporal Processing by Growth Factors in Memory Formation
记忆形成中生长因子的时间处理
- 批准号:
10521305 - 财政年份:2020
- 资助金额:
$ 47.64万 - 项目类别:
Temporal Processing by Growth Factors in Memory Formation
记忆形成中生长因子的时间处理
- 批准号:
10091527 - 财政年份:2020
- 资助金额:
$ 47.64万 - 项目类别:
Synaptic and Nuclear Signaling in Memory Formation
记忆形成中的突触和核信号传导
- 批准号:
7619962 - 财政年份:2007
- 资助金额:
$ 47.64万 - 项目类别:
Synaptic and Nuclear Signaling in Memory Formation
记忆形成中的突触和核信号传导
- 批准号:
7802316 - 财政年份:2007
- 资助金额:
$ 47.64万 - 项目类别:
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