Brain-wide circuits for drug-induced changes to cognition
药物引起的认知变化的全脑回路
基本信息
- 批准号:10494006
- 负责人:
- 金额:$ 30.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAnimalsBehaviorBehavioralBrainBrain regionCell NucleusCodeCognitionCognitiveComplexDissociationDrug AddictionDrug usageElectrophysiology (science)EnvironmentGeneticHCN1 channelHCN1 geneHippocampusImpairmentKetamineKnock-outKnockout MiceLeftLinkLocationLong-Term EffectsMeasuresMedialMemoryMethamphetamineMolecularMolecular TargetMorphineMovementMusNR2A NMDA receptorNatureNeuronsParietalPersonsPharmaceutical PreparationsPhysiologicalPositioning AttributePrevalencePropertyRelapseRewardsRunningSiteSpace PerceptionSpeedSystemTechniquesTechnologyTherapeuticTherapeutic AgentsTrainingUpdateViralVisualWorkbrain behaviorcognitive processdrug actiondrug of abusedrug seeking behaviorentorhinal cortexexperiencehypnoticin vivoinsightinterestneuralneural circuitneural correlateoperationpsychologicresponsespatial memoryvirtual reality environmentway finding
项目摘要
PROJECT SUMMARY (Project 2)
Dissociative and non-dissociative drugs, such as ketamine, PCP, methamphetamine and morphine, exert
powerful psychological effects by inducing profoundly altered brain states. The popularity of these drugs, their
psychologically and physiologically addictive nature and the rising prevalence of a subclass of dissociative drugs
as potential therapeutic agents indicate an urgent need to understand the acute and long-term effects of these
drugs on brain-states. A large gap exists however, in our understanding of the circuit mechanisms underlying
drug-altered states themselves. To bridge this gap, we seek to elucidate the molecular, circuit and network
mechanisms of drug induced cognitive states by taking advantage of a set of highly tractable response properties
of neurons across the multiple brain regions that support spatial cognition. Our focus on spatial cognition is
motivated by the shared capability of dissociative and non-dissociative drugs to alter neural representations of
space. Dissociative drugs are well documented to induce out-of-body experiences and can impair spatial
memory. Non-dissociative drugs of abuse can leverage the spatial memory system to encode drug-context
associations, leading to drug-associated contexts serving as a potent trigger for relapse to drug use. However,
the brain-wide circuit mechanisms underlying these alterations in spatial cognition, as well as how this impacts
behavior, remain incompletely understood. Here, we use cutting-edge large scale in vivo electrophysiology
combine with behavioral techniques to examine the link between drug-induced spatial cognitive effects and the
microcircuits of spatial and memory coding. First, we perform wide-scale electrophysiology to measure the
neural correlates of spatial estimates in multiple cortical and sub-cortical brain regions during navigation to
investigate how dissociative and non-dissociative drugs induce changes in spatial cognition. Next, we hone in
on particular brain regions of interest in freely moving animals to examine how dissociative and non-dissociative
drugs drive changes in the neural correlates of behavior in spatial tasks. Finally, in vivo electrophysiology is
combined with genetic and behavioral approaches to parse out the molecular basis of ketamine’s potentially
therapeutic versus negative effects on spatial cognition. Together, this work will provide new insight regarding
the brain wide-circuit mechanisms for cognitive states associated with drugs of addiction and the behavioral
impacts of these drug-induced cognitive states on spatial memory and navigational behavior.
.
项目概要(项目2)
解离性和非解离性药物,如氯胺酮、PCP、甲基苯丙胺和吗啡,
通过诱导大脑状态的深刻改变而产生强大的心理效应。这些药物的流行,
心理和生理上的成瘾性以及一种分裂性药物的流行率不断上升
由于潜在的治疗剂表明迫切需要了解这些药物的急性和长期影响,
药物对大脑状态的影响然而,在我们对电路机制的理解中存在很大的差距,
毒品改变了自己。为了弥合这一差距,我们试图阐明分子,电路和网络
利用一组高度易处理的反应特性研究药物诱导认知状态的机制
神经元在支持空间认知的多个大脑区域中的分布。我们对空间认知的关注是
动机是解离性和非解离性药物的共同能力,以改变神经表征,
空间有充分的证据表明,解离性药物可诱导灵魂出窍,并可损害空间记忆。
记忆非分离性药物滥用可以利用空间记忆系统对药物背景进行编码
这些关联导致与毒品有关的情况成为吸毒复吸的一个有力触发因素。然而,在这方面,
这些空间认知改变背后的全脑电路机制,以及这如何影响
行为,仍然不完全理解。在这里,我们使用尖端的大规模体内电生理学
联合收割机与行为技术相结合,以检查药物诱导的空间认知效应与
空间和记忆编码的微电路首先,我们进行大范围的电生理学测量,
导航期间多个皮层和皮层下脑区域中空间估计的神经相关性,
研究解离性和非解离性药物如何诱导空间认知的变化。接下来,
在自由活动的动物的特定大脑区域,研究解离性和非解离性
药物驱动空间任务中行为的神经相关物的变化。最后,体内电生理学是
结合遗传学和行为学的方法来分析氯胺酮潜在的分子基础,
对空间认知的治疗和负面影响。总之,这项工作将提供新的见解,
药物成瘾认知状态的脑宽回路机制和药物成瘾行为的脑宽回路机制
这些药物诱导的认知状态对空间记忆和导航行为的影响。
.
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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Lisa Giocomo其他文献
Lisa Giocomo的其他文献
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{{ truncateString('Lisa Giocomo', 18)}}的其他基金
The Dynamics of Neural Representations for Distinct Spatial Contexts and Memory Episodes
不同空间背景和记忆片段的神经表征的动力学
- 批准号:
10620709 - 财政年份:2022
- 资助金额:
$ 30.13万 - 项目类别:
The Dynamics of Neural Representations for Distinct Spatial Contexts and Memory Episodes
不同空间背景和记忆片段的神经表征的动力学
- 批准号:
10435250 - 财政年份:2022
- 资助金额:
$ 30.13万 - 项目类别:
Mesh electronics for understanding space encoding in the amphibian brain
用于理解两栖动物大脑空间编码的网状电子器件
- 批准号:
10446284 - 财政年份:2022
- 资助金额:
$ 30.13万 - 项目类别:
Research Project 4 - Internal state dynamics of navigation and memory
研究项目4 - 导航和记忆的内部状态动力学
- 批准号:
10687148 - 财政年份:2021
- 资助金额:
$ 30.13万 - 项目类别:
Research Project 4 - Internal state dynamics of navigation and memory
研究项目4 - 导航和记忆的内部状态动力学
- 批准号:
10490244 - 财政年份:2021
- 资助金额:
$ 30.13万 - 项目类别:
Research Project 4 - Internal state dynamics of navigation and memory
研究项目4 - 导航和记忆的内部状态动力学
- 批准号:
10047735 - 财政年份:2021
- 资助金额:
$ 30.13万 - 项目类别:
The Ionic Basis of Spatial Codes in Medial Entorhinal Cortex
内侧内嗅皮层空间编码的离子基础
- 批准号:
9321962 - 财政年份:2015
- 资助金额:
$ 30.13万 - 项目类别:
Spatial Codes Across the Medial Entorhinal Cortex for Memory and Navigation
内侧内嗅皮层用于记忆和导航的空间代码
- 批准号:
10120754 - 财政年份:2015
- 资助金额:
$ 30.13万 - 项目类别:
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