Circuitry dynamics underlying opioid-dependence: Integrating structural, functional, and transcriptomic mechanisms
阿片类药物依赖性的电路动力学:整合结构、功能和转录组机制
基本信息
- 批准号:10838996
- 负责人:
- 金额:$ 5.97万
- 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:2022-09-01 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:AbstinenceAccelerationAddressAdoptedAnatomyArchitectureBrainBrain regionCell NucleusCellsChronicData SetDependenceDevelopmentFutureGene ExpressionGenesHeadIn Situ HybridizationLabelLinkMaintenanceMapsMeasurementMethodsMicroscopeNeuroanatomyNeuronsOpiate AddictionOpioid PeptideOpioid ReceptorProcessRelapseResearchResearch PersonnelResolutionTherapeuticTimeTissuesWithdrawaladdictioncell typecontrol theoryendogenous opioidsimprovedneural circuitneuroimagingopioid exposureopioid withdrawalresponsesearchable databasetranscriptomicsvirus genetics
项目摘要
PROJECT SUMMARY
A range of cellular and circuit-level adaptations develops in response to chronic opioid exposure, which are
strongly linked to several facets of opioid addiction: tolerance, withdrawal and processes that may contribute to
compulsive use and relapse. However, we still do not have a comprehensive picture of the dynamic connections
and activities of neuronal networks in the brain that express the opioid receptors and peptides. Therefore, a
critical need exists to map the global cell-type identity, transcriptomic trajectory, shifting connectivity, and
ensemble activity of the key opioidergic networks underlying the onset and maintenance of cellular dependence,
and withdrawal. This proposal aims to investigate the architecture and function of endogenous MOR-expressing
neural circuits in key cortical and subcortical brain regions, in order to determine how these circuits maintain
cellular dependence and drive brain-wide maladaptive plasticity across different stages of the OUD cycle. In four
complementary aims, we will first map the shifting structural and functional connectivity of opioidergic networks
using viral-genetic and tissue clearing methods to identify monosynaptic inputs to all MOR-expressing, as well
as withdrawal-active MOR-expressing neurons, as a function of opioid exposure and abstinence. We will then
integrate these dynamic neuroanatomical maps with cell-type information and gene expression changes by
combing single-nuclei sequencing and spatial cellular-resolution transcriptomics via hyper-multiplexed in situ
hybridizations to generate the anatomic localization of hundreds of dependence-related genes, targeted to cell
types and retro-labeled connections. Lastly, to reveal how MOR-expressing cells within the cortical and
subcortical target regions are modulated during opioid exposure in real-time, we will use miniature head-mounted
microscopes to image the neural ensemble activities across weeks of opioid exposure and withdrawal. To bridge
these experimental measurements and provide a common framework for our analyses, we will adopt Network
Control Theory to identify brain nodes that drive the transition between opioid dependence states to identify
potential candidates that disproportionately drive each state. Our datasets will provide formal summaries and a
publicly available, searchable database logging the activity, connectivity, and gene expression as they evolve
with repetitive opioid exposure, withdrawal, and abstinence.
项目总结
项目成果
期刊论文数量(1)
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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KEVIN T BEIER其他文献
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{{ truncateString('KEVIN T BEIER', 18)}}的其他基金
Circuitry dynamics underlying opioid-dependence: Integrating structural, functional, and transcriptomic mechanisms
阿片类药物依赖性的电路动力学:整合结构、功能和转录组机制
- 批准号:
10509750 - 财政年份:2022
- 资助金额:
$ 5.97万 - 项目类别:
Investigation of neural ensembles driving pain chronification
驱动疼痛慢性化的神经系统的研究
- 批准号:
10841343 - 财政年份:2022
- 资助金额:
$ 5.97万 - 项目类别:
Investigation of neural ensembles driving pain chronification
驱动疼痛慢性化的神经系统的研究
- 批准号:
10567552 - 财政年份:2022
- 资助金额:
$ 5.97万 - 项目类别:
INVESTIGATING FUNCTION OF NOVEL DRUG-INDUCED SYNAPTIC CHANGES IN THE VTA
研究新型药物引起的 VTA 突触变化的功能
- 批准号:
10000906 - 财政年份:2018
- 资助金额:
$ 5.97万 - 项目类别:
INVESTIGATING FUNCTION OF NOVEL DRUG-INDUCED SYNAPTIC CHANGES IN THE VTA
研究新型药物引起的 VTA 突触变化的功能
- 批准号:
9769671 - 财政年份:2018
- 资助金额:
$ 5.97万 - 项目类别:
Investigating function of novel drug-induced synaptic changes in the VTA
研究新型药物诱导的 VTA 突触变化的功能
- 批准号:
9086583 - 财政年份:2016
- 资助金额:
$ 5.97万 - 项目类别:
Elucidating input-output relations of rewarding and aversive VTA dopamine neurons
阐明奖励性和厌恶性 VTA 多巴胺神经元的输入输出关系
- 批准号:
8832974 - 财政年份:2015
- 资助金额:
$ 5.97万 - 项目类别:
Viral tracing of genetically defined neural circuitry
基因定义的神经回路的病毒追踪
- 批准号:
8206536 - 财政年份:2010
- 资助金额:
$ 5.97万 - 项目类别:
Viral tracing of genetically defined neural circuitry
基因定义的神经回路的病毒追踪
- 批准号:
8020049 - 财政年份:2010
- 资助金额:
$ 5.97万 - 项目类别:
Viral tracing of genetically defined neural circuitry
基因定义的神经回路的病毒追踪
- 批准号:
7809977 - 财政年份:2010
- 资助金额:
$ 5.97万 - 项目类别:
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