Temporal dynamics of Arc (Arg3.1) transcriptional regulation
Temporal dynamics of Arc (Arg3.1) transcriptional regulation
批准号:
10370358
负责人:
Sulagna Das
金额:
$25.2万
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:
已结题
起止时间:
2021-03-15 至 2024-02-29
关键词:
AcuteAffectAllelesAlzheimer&aposs DiseaseAreaBacteriophagesBehaviorCell NucleusCellsChIP-seqCollaborationsComplexCouplingDataDependenceDiseaseEarly Gene TranscriptionsElementsEnsureEventFeedbackFrequenciesGene ExpressionGene Expression RegulationGene ProteinsGenesGenetic TranscriptionGenomeGenomicsGlutamatesHeterogeneityHippocampus (Brain)HourImageImmediate-Early GenesImpairmentIndividualKineticsKnock-in MouseLabelLearningLettersLinkMaintenanceMapsMediatingMemoryMemory impairmentMental disordersMessenger RNAMolecularNeuronsNeurosciencesNuclearPatternPeriodicityProbabilityProcessProtein BiosynthesisProteinsRNA chemical synthesisRegulationReporterRoleSchizophreniaSignal TransductionSliceSynapsesSynaptic TransmissionTestingTimeTimeLineTrainingTranscriptional RegulationTranslatingTranslationsautism spectrum disorderbasebehavioral responsechromatin remodelingcognitive functioncognitive performancecognitive processcombinatorialdentate gyrusdesigndetection sensitivityexperiencegranule cellimprovedinsightinterestknock-downlong term memorymRNA Exportmemory consolidationmouse modelnervous system disorderneuronal circuitryneuronal patterningnoveloptogeneticspromoterreal-time imagesreceptorresponsespatial memoryspatiotemporalstemtemporal measurementtranscription factortranscriptomics
中文摘要
文摘:
英文摘要
Abstract:
Deficits in learning and memory are hallmarks of several psychiatric disorders including
schizophrenia, autism, and Alzheimer’s. These cognitive processes in both normal and disease
states are controlled by spatiotemporally regulated genes in neuronal circuits. Studies have
implicated the role of immediate-early genes (IEGs), particularly, Activity-regulated cytoskeletal
associated (Arc/Arg3.1) in behavioral responses. Arc has garnered special interest because it
affects synaptic transmission, plasticity and long-term memory. The conversion from short-term
to long-term memory, a process known as consolidation, requires Arc protein levels to be
maintained over several hours to days. However, existing studies indicate very short half-lives of
Arc mRNA and protein (less than 60 mins). It is intriguing how short temporal window of Arc
expression promotes memory consolidation over long time scales. For IEGs including Arc, the
regulation of gene expression initiates at the level of transcription. Therefore, we hypothesize that
periodic cycles of transcription in a subset of neurons would enable persistence of Arc levels in
the network for stabilizing the memory trace. We propose to identify the molecular mechanisms
underlying these transcription cycles. Recently, we have generated a knock-in mouse model
where the endogenous Arc gene is fluorescently labeled with bacteriophage-derived stem loops,
enabling high detection sensitivity and imaging of individual Arc alleles in single neurons over
several hours with unprecedented temporal resolution. By real-time imaging of endogenous Arc
gene transcription in cultured neurons and in acute hippocampal slices, we will establish the long-
term Arc transcription dynamics and its dependence on patterns of neuronal activity. We will
characterize the role of activity and translational feedback in Arc transcriptional regulation at
different time scales. This will provide insights into: i) how long term Arc transcriptional regulation
impacts memory consolidation and ii) improve design of activity-based reporters to reliably
correlate Arc expression and behavior.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
DOI:
10.3389/fcell.2021.663367
发表时间:
2021
期刊:
Frontiers in cell and developmental biology
影响因子:
5.5
作者:
[Kharod SC, Hwang DW, Das S, Yoon YJ]
通讯作者:
Yoon YJ
Mechanism of mRNA Localization and Localized Translation in Neurons
-
批准号:10708979
-
项目类别:
-
资助金额:$67.63万
-
财政年份:1992
-
负责人:Sulagna Das
-
依托单位:
Mechanism of mRNA Localization and Localized Translation in Neurons
-
批准号:10586910
-
项目类别:
-
资助金额:$66.58万
-
财政年份:1992
-
负责人:Sulagna Das
-
依托单位:
海外基金