Neural circuit dynamics of drug action

总体汇总 我们将开发一个NIDA中心，药物作用的神经回路动力学，致力于开发， 应用和传播药物引起的改变状态的全脑和细胞分辨率分析 虐待我们的科学将集中在确定因果电路水平的行动，滥用药物，在调节 与环境、风险和回报评估相关的行为。以一种将合作者聚集在一起的方式 我们专注于具有不同分子特征但共享的临床重要药物， 对理解与社会和非社会风险和回报相关的行为和感知的重要性。 在经验证的人体环境中，使用的具体药物包括甲基苯丙胺、MDMA和氯胺酮， 大鼠和小鼠的社会和非社会行为。我们将开发全脑技术， 与NIDA IRP及其他机构一起开展广泛的外联、培训和教育，以扩大影响。中心 包括四个研究项目（1：由Karl Deisseroth博士领导，重点是甲基苯丙胺，MDMA和 氯胺酮在小鼠和大鼠的皮质和大脑中的作用; 2：由丽莎乔科莫博士领导，专注于 甲基苯丙胺和氯胺酮在小鼠和大鼠的内嗅皮层和海马结构中的作用; 3： 由Robert Malenka博士领导，专注于甲基苯丙胺和MDMA在小鼠大脑中的作用;以及4： 由Leanne威廉姆斯博士和Brian Knutson博士领导，专注于与人体结构和功能成像相关的 甲基苯丙胺，氯胺酮，摇头丸，以及风险/回报关系。广泛而多样的互动， 这些小组和外部合作者将通过中心的重要培训核心得到进一步充实， 传播这些技术以推进药物滥用研究，这是开发下一个- 适用于药物滥用研究的生成技术，以及 协调这些重要的互动。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，从分子和突触到电路和行为， 完整人脑的范围，因为我们确定了动物体内的相关结构-活动关系， 人类神经系统

Overall Summary We will develop a NIDA Center, Neural circuit dynamics of drug action, 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, rat, and mouse social and nonsocial behaviors. We will both 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 brain of mice and rats; 2: led by Dr. Lisa Giocomo, focusing on methamphetamine and ketamine action in entorhinal cortex and hippocampal formation of mice and rats; 3: led by Dr. Robert Malenka, focusing on methamphetamine and MDMA action across the brain of mice; and 4: led by Dr. Leanne Williams and Brian Knutson, focusing on human structural and functional imaging relevant to methamphetamine, ketamine, MDMA, and risk/reward relationships. Broad and diverse interactions among these 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.