Generation of a dual transgenic/viral system to characterize multiple engrams in a single mouse
生成双转基因/病毒系统来表征单个小鼠中的多个印迹
基本信息
- 批准号:10541354
- 负责人:
- 金额:$ 4.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAlzheimer&aposs DiseaseAutomobile DrivingBehavioralBiologicalBrainBrain regionCellsChemicalsComputer ModelsComputing MethodologiesDevelopmentDiseaseDoxycyclineElectrophysiology (science)EngineeringEnvironmentExhibitsExposure toGenerationsGeneticGoalsHippocampus (Brain)Immediate-Early GenesKnowledgeLabelLaboratoriesLaboratory StudyLatinaLearningMeasuresMemoryMemory DisordersModernizationMouse ProteinMusNeurobiologyNeuronal DysfunctionNeuronsPatternPhasePopulationPopulation DynamicsPositioning AttributePropertyResearchResearch PersonnelResearch Project GrantsResearch ProposalsRoleScientistStimulusSynapsesSystemTechniquesTestingTimeTrainingTransgenic OrganismsViralWhole-Cell Recordingscareercombinatorialcomputerized toolsconditioned feardentate gyrusexperiencein vivomemory encodingmemory processmemory retrievalneurobiological mechanismnew technologynovelrecruitrelating to nervous systemskillstool
项目摘要
PROJECT SUMMARY / ABSTRACT
Memories are thought to be stored through lasting physical and chemical changes in the brain. The biological
substrate of a memory is known as an engram or memory trace. An engram is the neural ensemble activated
during learning and whose reactivation by the original stimulus results in memory retrieval. Modern
technological advances have allowed scientists to visualize and manipulate engrams, showing that they exist
in various brain regions and their content can be altered. These strategies have taken advantage of immediate
early genes (IEGs) such as Arc, which are expressed upon neuronal activation. Transgenic and viral tools,
such as the ArcCreERT2 mice and the Robust Activity Marking (RAM) system, have been engineered to label
cells in an activity-dependent manner. Although these tools have furthered our understanding of how a single
engram is represented in the brain, they have not been combined to label multiple engrams. Thus, this
research plan focuses on identifying multiple engrams in a single mouse and characterizing the synaptic
mechanisms underlying multiple engram storage. To achieve these goals, I have developed and characterized
a novel viral strategy that allows for the labeling of previously activated Arc+ ensembles. I have combined this
viral strategy with the ArcCreERT2 x enhanced yellow fluorescent protein (EYFP) mice to ultimately label
multiple Arc+ ensembles and visualize multiple engrams in a single mouse. Using this novel combinatorial
transgenic/viral strategy, I have shown that the engrams of exposures to a single environment are reactivated
to a greater extent those representing exposures to different environments. Moreover, the synaptic
mechanisms that contribute to the storage of multiple memories in the hippocampus is poorly understood. To
this end, during the F99 phase, I propose to use ex vivo electrophysiology to identify synaptic signatures (e.g.,
excitability, connectivity) of co-labeled Arc+ ensembles. A greater understanding of the synaptic properties of
the ensembles that are recruited to multiple engrams will contribute to our overall understanding of how
memories are co-stored in the brain. For the K00 phase, I will investigate the population-level dynamics of
hippocampal ensembles during memory processes using large-scale recording techniques and computational
models. These studies will illuminate our understanding of the computations performed by the hippocampus
that support memory processes and will allow us to generate more precise hypotheses for how these
computations might go awry in memory-related disorders, such as Alzheimer’s Disease (AD). The completion
of this research proposal will provide me with training in electrophysiology, strengthen my technical and
professional skills, and facilitate my transition to a postdoctoral position in a laboratory that studies population
dynamics of neural ensembles and computational methods.
项目摘要/摘要
记忆被认为是通过大脑中持久的物理和化学变化来储存的。生物学的
存储器的衬底被称为印迹或存储器迹线。印记是激活的神经集合。
在学习过程中,其被原始刺激重新激活会导致记忆提取。现代
技术的进步使科学家能够可视化和操控铭文,表明它们的存在
在不同的大脑区域,它们的内容可以改变。这些战略利用了眼前的优势
早期基因(IEG),如Arc,在神经元激活时表达。转基因和病毒工具,
例如ArcCreERT2小鼠和健壮活动标记(RAM)系统,已经被设计成标记
细胞以一种依赖活动的方式。尽管这些工具加深了我们对单个
字母在大脑中被代表,它们还没有被组合来标记多个字母。因此,这一点
研究计划的重点是在一只小鼠身上识别多个字母,并表征突触
多重印记存储的潜在机制。为了实现这些目标,我开发并刻画了
一种新的病毒策略,允许标记先前激活的Arc+系综。我把这个组合在一起
用ArcCreERT2 x增强型黄色荧光蛋白(EYFP)小鼠的病毒策略最终标记
多个Arc+合奏,并在一个鼠标中可视化多个字母。利用这种新颖的组合
转基因/病毒策略,我已经证明了暴露在单一环境中的印记被重新激活
在更大程度上,那些代表暴露在不同环境中的人。此外,突触
在海马体中存储多个记忆的机制还知之甚少。至
为此,在F99阶段,我建议使用体外电生理学来识别突触信号(例如,
共同标记的Arc+系综的兴奋性、连接性)。对神经元突触特性有更深入的了解
被招募到多个字母组的乐团将有助于我们对如何
记忆被共同储存在大脑中。对于K00阶段,我将调查以下人口级别的动态
使用大规模记录技术和计算技术的记忆过程中的海马群
模特们。这些研究将阐明我们对海马体执行的计算的理解
支持记忆过程,并将允许我们产生更精确的假设
在与记忆相关的疾病中,例如阿尔茨海默病(AD),计算可能会出错。完成度
这项研究提案将为我提供电生理学方面的培训,加强我的技术和
专业技能,并帮助我过渡到一个研究人口的实验室的博士后职位
神经系综动力学和计算方法。
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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Michelle Stackmann其他文献
Michelle Stackmann的其他文献
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{{ truncateString('Michelle Stackmann', 18)}}的其他基金
Generation of a dual transgenic/viral system to characterize multiple engrams in a single mouse
生成双转基因/病毒系统来表征单个小鼠中的多个印迹
- 批准号:
10670679 - 财政年份:2022
- 资助金额:
$ 4.78万 - 项目类别: