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：
Lisa Giocomo
金额：
$ 30.13万
依托单位：
STANFORD UNIVERSITY
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：
https://reporter.nih.gov/project-details/10494006
关键词：
Acute Animals Behavior Behavioral Brain Brain region Cell Nucleus Code Cognition Cognitive Complex Dissociation Drug Addiction Drug usage Electrophysiology (science)Environment Genetic HCN1 channel HCN1 gene Hippocampus Impairment Ketamine Knock-out Knockout Mice Left Link Location Long-Term Effects Measures Medial Memory Methamphetamine Molecular Molecular Target Morphine Movement Mus NR2A NMDA receptor Nature Neurons Parietal Persons Pharmaceutical Preparations Physiological Positioning Attribute Prevalence Property Relapse Rewards Running Site Space Perception Speed System Techniques Technology Therapeutic Therapeutic Agents Training Update Viral Visual Work brain behavior cognitive process drug action drug of abuse drug seeking behavior entorhinal cortex experience hypnotic in vivo insight interest neural neural circuit neural correlate operation psychologic response spatial memory virtual reality environment way 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. .

项目摘要（项目2）氯胺酮，pcp，甲基苯丙胺和吗啡等分离和非分离药物执行诱发的大脑状态发生了强大的心理影响。这些药物的普及在心理和身体上加性的性质以及分离药物子类的普遍性由于潜在的治疗剂表明迫切需要了解这些的急性和长期影响在脑状态上的毒品。但是，存在很大的差距，在我们对电路机制的理解中改变毒品的状态本身。为了弥合这一差距，我们试图阐明分子，电路和网络通过利用一组高度可拖动的响应特性，药物诱导认知状态的机制支持空间认知的多个大脑区域的神经元。我们对空间认知的关注是由分离和非分离药物的共同能力的共同能力改变了改变的神经表征空间。分离药物有充分的文献记录以诱导身体外的体验，并且会损害空间记忆。滥用的非分离药物可以利用空间记忆系统来编码毒品秘密协会，导致与药物相关的环境，这是一种潜在的触发药物使用的触发因素。然而，这些改变空间认知改变的脑电路机制，以及这如何影响行为，保持不完全理解。在这里，我们使用尖端的大规模体内电生理学结合行为技术，以检查药物诱导的空间认知效应与空间和内存编码的微电路。首先，我们执行大规模的电生理学来测量导航期间多皮质和亚皮质脑区域中空间估计值的神经相关性研究解离性和非分离性药物如何诱导空间认知的变化。接下来，我们在在自由移动动物的特定大脑区域中，以检查分离和非分离的方式药物驱动空间任务中行为的神经元相关性的变化。最后，体内电生理学是结合遗传和行为方法，解析氯胺酮潜在的分子基础治疗与负面影响的负面影响。这项工作将共同提供有关的新见解与成瘾药物相关的认知状态的大脑宽电路机制和行为这些药物引起的认知状态对空间记忆和航行行为的影响。。