Transcriptional, functional, and circuit profiling at single cell resolution of neuronal ensembles engaged by heroin relapse
海洛因复吸所涉及的神经元群的单细胞分辨率转录、功能和回路分析
基本信息
- 批准号:10292403
- 负责人:
- 金额:$ 56.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAnatomyAnimal BehaviorAnimal ModelAtlasesBehaviorBioinformaticsBiological AssayBrainBrain regionCalciumCellsChromatinCommunitiesCuesDataData CollectionData SetDevelopmentDorsalDrug ExposureDrug ModelingsDrug usageExposure toFluorescent in Situ HybridizationFutureGene ExpressionGene Expression ProfileGene Expression ProfilingGenesGenetic TranscriptionGoldHeroinHeroin DependenceHumanImageIndividualIndividual DifferencesInfusion proceduresKnowledgeLeadLightMeasurementMedialMicroscopyModelingMolecularNatureNervous system structureNeuronsNeurosciencesNucleus AccumbensOpiate AddictionOpioidPatternPharmaceutical PreparationsPopulationProcessPublishingRNARattusRelapseResearchResolutionResourcesSamplingSelf AdministrationSeriesSignal TransductionSliceSocietiesStandardizationSystemThalamic structureTissue-Specific Gene ExpressionTissuesaddictionbasebehavioral phenotypingbrain cellbrain tissuecell typecohortdrug developmentdrug seeking behaviorin vivoin vivo calcium imagingmolecular markerneural circuitnovelopioid userelating to nervous systemresponsesingle cell sequencingsingle-cell RNA sequencingtherapeutic candidatetherapeutic target
项目摘要
Abstract:
Opiate addiction extorts a tremendous toll on society, but a mechanistic understanding of how repeated exposure
to opioids such as heroin ultimately results in compulsive drug-taking and -seeking behavior in some individuals,
but not others, is still not known. A longstanding idea is that enduring changes in neural circuit function occur
because of drug-induced gene expression changes in certain brain cells. This facilitates subsequent drug-taking
and -seeking behaviors in vulnerable individuals. Unfortunately, identifying cell-type specific alterations following
drug use (typically performed in established animal models of addiction), is generally a slow and tedious process
as changes in gene expression following in vivo drug exposure are typically assayed in series, within
heterogeneous brain regions, in an a-priori hypothesis driven fashion (i.e. previous knowledge predicting a
specific gene may be involved). This dramatically limits the throughput of data collection and likely complicates
the subsequent interpretation as gene expression patterns data are typically captured from thousands to millions
of homogenized cells. Given that the nervous system is composed of highly heterogeneous tissue, re-assessing
cell type specific gene expression changes in an unbiased manner from 1000's of individual cells is desperately
needed. Here, we propose to combine our expertise in order to generate comprehensive datasets aimed at
understanding how single-cell gene expression, circuit connectivity, and neural activity patterns are impacted by
previous drug-taking behavior. These data will provide a much-needed cellular atlas and resource for the
addiction neuroscience community and will likely lead to the identification of many novel cell type, gene
expression changes, and ensembles that can be leveraged for future study.
抽象的:
阿片成瘾对社会造成巨大损失,但对重复接触阿片成瘾的机制有一个机械性的理解
海洛因等阿片类药物最终会导致某些人出现强迫性吸毒和寻求毒品的行为,
但不是其他人,目前还不得而知。一个长期存在的想法是神经回路功能会发生持久的变化
因为药物诱导某些脑细胞的基因表达发生变化。这有利于后续吸毒
- 寻求弱势个体的行为。不幸的是,识别细胞类型特异性改变如下
吸毒(通常在已建立的成瘾动物模型中进行)通常是一个缓慢而乏味的过程
因为体内药物暴露后基因表达的变化通常是连续进行的,在
异质的大脑区域,以先验假设驱动的方式(即先前的知识预测
可能涉及特定基因)。这极大地限制了数据收集的吞吐量,并可能使数据收集变得复杂
随后的解释为基因表达模式数据通常捕获数千到数百万
匀浆细胞。鉴于神经系统是由高度异质的组织组成,重新评估
细胞类型特异性基因表达以无偏见的方式从数千个个体细胞中发生变化是迫切需要的
需要。在这里,我们建议结合我们的专业知识,生成旨在
了解单细胞基因表达、回路连接和神经活动模式如何受到影响
既往吸毒行为。这些数据将为人类提供急需的细胞图谱和资源。
成瘾神经科学界可能会导致许多新的细胞类型、基因的鉴定
表达变化以及可用于未来研究的集合。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Susan Marie Ferguson其他文献
Susan Marie Ferguson的其他文献
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{{ truncateString('Susan Marie Ferguson', 18)}}的其他基金
Characterization of cortical neuronal subtypes in cocaine self-administration
可卡因自我给药皮质神经元亚型的特征
- 批准号:
10815221 - 财政年份:2023
- 资助金额:
$ 56.99万 - 项目类别:
Assessing the role of corticostriatal circuitry in polysubstance use of fentanyl and methamphetamine using rat self-administration models
使用大鼠自我给药模型评估皮质纹状体回路在芬太尼和甲基苯丙胺多物质使用中的作用
- 批准号:
10737092 - 财政年份:2023
- 资助金额:
$ 56.99万 - 项目类别:
Characterization of cortical neuronal subtypes in cocaine self-administration
可卡因自我给药皮质神经元亚型的特征
- 批准号:
10893672 - 财政年份:2023
- 资助金额:
$ 56.99万 - 项目类别:
University of Washington Significant Opportunities in Addiction Research (UW-SOAR) Neuroscience Doctoral Readiness Program
华盛顿大学成瘾研究的重大机会(UW-SOAR)神经科学博士准备计划
- 批准号:
10706601 - 财政年份:2022
- 资助金额:
$ 56.99万 - 项目类别:
University of Washington Significant Opportunities in Addiction Research (UW-SOAR) Neuroscience Doctoral Readiness Program
华盛顿大学成瘾研究的重大机会(UW-SOAR)神经科学博士准备计划
- 批准号:
10610060 - 财政年份:2022
- 资助金额:
$ 56.99万 - 项目类别:
Transcriptional, functional, and circuit profiling at single cell resolution of neuronal ensembles engaged by heroin relapse
海洛因复吸所涉及的神经元群的单细胞分辨率转录、功能和回路分析
- 批准号:
10434119 - 财政年份:2021
- 资助金额:
$ 56.99万 - 项目类别:
Transcriptional, functional, and circuit profiling at single cell resolution of neuronal ensembles engaged by heroin relapse
海洛因复吸所涉及的神经元群的单细胞分辨率转录、功能和回路分析
- 批准号:
10596142 - 财政年份:2021
- 资助金额:
$ 56.99万 - 项目类别:
Characterization of cortical neuronal subtypes in cocaine self-administration
可卡因自我给药皮质神经元亚型的特征
- 批准号:
10413029 - 财政年份:2019
- 资助金额:
$ 56.99万 - 项目类别:
Characterization of cortical neuronal subtypes in cocaine self-administration
可卡因自我给药皮质神经元亚型的特征
- 批准号:
10350049 - 财政年份:2019
- 资助金额:
$ 56.99万 - 项目类别:
Characterization of cortical neuronal subtypes in cocaine self-administration
可卡因自我给药皮质神经元亚型的特征
- 批准号:
10627077 - 财政年份:2019
- 资助金额:
$ 56.99万 - 项目类别:
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