Neural circuit dynamics of drug action:revealing, uncoupling, and restoring altered brain states

项目概要（总体） 我们在这里描述的愿景和计划的第二个五年期的支持NIDA中心， 卓越，药物作用的神经回路动力学。该中心致力于发展， 应用和传播的全脑和细胞分辨率分析的改变状态引起的 滥用药物。我们的科学将集中在确定滥用药物的因果电路水平的行动， 调节与环境、风险和回报评估相关的行为。在某种程度上， 中心的合作小组，我们专注于具有不同分子的临床重要药物， 个人资料，但共同的意义，了解行为和看法有关的社会和 非社会性的风险和回报。使用的具体药剂包括甲基苯丙胺、MDMA和氯胺酮， 在人类和啮齿动物的社会和非社会行为的验证设置。我们将开发 全脑技术，并参与广泛的推广，培训和教育，以扩大影响， 与NIDA IRP及其他机构合作。该中心包括四个研究项目（1：由卡尔博士领导 Deisseroth，专注于甲基苯丙胺，MDMA和氯胺酮在皮层和整个大脑中的作用， 小鼠大脑; 2：由丽莎Giocomo博士领导，专注于甲基苯丙胺和氯胺酮的作用， 小鼠的内嗅皮层和海马结构; 3：由Robert Malenka博士和Boris Heiden博士领导， 专注于甲基苯丙胺和MDMA在小鼠大脑中的作用; 4：由Leanne博士领导 威廉姆斯和布赖恩克努森博士，专注于人体结构和功能成像相关的， 甲基苯丙胺、氯胺酮、摇头丸和风险/回报关系。广泛而多样的互动 这些团体和外部合作者将通过中心的重要培训进一步丰富 传播这些技术以推进药物滥用研究的核心， 发展适合应用于药物滥用研究的新一代科技，以及 协调这些重要互动的管理核心。NIDA中心的这种方法 将使我们能够利用我们团队的独特优势，跨越分子和 突触，电路和行为，达到完整的人类大脑的范围，因为我们确定相关的 动物和人类神经系统中的结构-活性关系。

PROJECT SUMMARY (Overall) We describe here the vision and plan for the second five-year period of support for a NIDA Center of Excellence, Neural circuit dynamics of drug action. This Center is dedicated to the development, application, and dissemination of brainwide and cellular-resolution analyses of altered states elicited by drugs of abuse. Our science will focus on identifying the causal circuit-level actions of drugs of abuse in modulating behavior relevant to assessment of context, risk and reward. In a manner that brings together the collaborating groups of the Center, we focus on clinically significant drugs with different molecular profiles but shared significance for understanding behaviors and perceptions relevant to social and nonsocial risk and reward. Specific agents employed include methamphetamine, MDMA, and ketamine, in the setting of validated human and rodent social and nonsocial behaviors. We will develop the brainwide technologies and engage in extensive outreach, training, and education to broaden impact, with the NIDA IRP and beyond. The Center includes four Research Projects (1: led by Dr. Karl Deisseroth, focusing on methamphetamine, MDMA and ketamine action in the cortex and across the brains of mice; 2: led by Dr. Lisa Giocomo, focusing on methamphetamine and ketamine action in entorhinal cortex and hippocampal formation of mice; 3: led by Dr. Robert Malenka and Dr. Boris Heifets, focusing on methamphetamine and MDMA action across the brain of mice; and 4: led by Dr. Leanne Williams and Dr. Brian Knutson, focusing on human structural and functional imaging relevant to methamphetamine, ketamine, MDMA, and risk/reward relationships. Broad and diverse interactions amongthese groups and external collaborators will be further enriched by the Center’s vital Training Core for disseminating these techniques to advance drug abuse research, a Technology Core for developing the next- generation technologies suitable for application to drug abuse research, and an Administrative Core for orchestrating these important interactions. This approach to the NIDA Center will allow us to capitalize on the unique strengths of our team, crossing scales from molecules and synapses, to circuits and behavior, reaching the scope of the intact human brain as we identify relevant structure-activity relationships within animal and human nervous systems.