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

项目总结(总体) 我们在这里描述了支持NIDA中心的第二个五年计划的愿景和计划 卓越，药物作用的神经回路动力学。这个中心致力于发展， 应用和传播脑部和细胞分辨率分析引起的改变状态 滥用药物。我们的科学将专注于识别滥用药物的因果电路水平的行为 调节与环境、风险和回报评估相关的行为。以一种将 该中心的合作小组，我们专注于不同分子的临床意义药物 个人资料，但对于理解与社会和 非社会风险和回报。使用的特定毒剂包括甲基苯丙胺、MDMA和氯胺酮， 在确认人类和啮齿动物的社会和非社会行为的背景下。我们将开发 全脑性技术，并广泛参与外展、培训和教育，以扩大影响， 与NIDA IRP和其他机构合作。该中心包括四个研究项目(1：由卡尔博士领导 重点研究了甲基苯丙胺、MDMA和氯胺酮在大脑皮层和大脑中的作用。 小鼠的大脑；2：由Lisa Giocomo博士领导，重点研究甲基苯丙胺和氯胺酮在 小鼠内嗅皮层和海马结构；3：由Robert Malenka博士和Boris Heifets博士领导， 专注于甲基苯丙胺和MDMA在小鼠大脑中的作用；和4：由Leanne博士领导 Williams和Brian Knutson博士，专注于与以下相关的人类结构和功能成像 甲基苯丙胺、氯胺酮、摇头丸和风险/回报关系。广泛多样的互动 中心的重要培训将进一步丰富这些小组和外部合作者 传播这些技术以促进药物滥用研究的核心， 开发适用于药物滥用研究的下一代技术，以及 用于协调这些重要交互的管理核心。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，与电路和行为，达到完整的人脑的范围，当我们识别相关的 动物和人类神经系统内的结构-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.