Neural circuit dynamics of drug action

总体摘要 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， 药物引起的状态改变的全脑和细胞分辨率分析的应用和传播 滥用职权。我们的科学将专注于识别滥用药物在调制过程中的因果电路水平行为 与评估背景、风险和回报相关的行为。以一种将合作 该中心的小组，我们专注于具有临床意义的药物，分子谱不同，但共享 对理解与社会和非社会风险和回报相关的行为和认知的意义。 使用的特定制剂包括甲基苯丙胺、MDMA和氯胺酮，在经验证的人的环境中， 老鼠，以及老鼠的社交和非社交行为。我们都将开发全脑技术，并参与 广泛的外联、培训和教育，以扩大与NIDA IRP及其他项目的影响。《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皮质和整个大脑中的作用；2：由Lisa Giocomo博士领导，重点是 甲基苯丙胺和氯胺酮在小鼠和大鼠内嗅皮层和海马区的作用；3： 由Robert Malenka博士领导，重点研究甲基苯丙胺和MDMA在小鼠大脑中的作用；以及4： 由Leanne Williams博士和Brian Knutson博士领导，专注于与人体结构和功能相关的成像 甲基苯丙胺、氯胺酮、摇头丸和风险/回报关系。之间广泛而多样的互动 中心的重要培训核心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，这是开发下一代- 适用于药物滥用研究的生成技术和管理核心 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，跨越了从分子和突触到电路和行为的范围，达到 当我们确定动物和动物体内相关的结构-活性关系时，完整人脑的范围 人类的神经系统。

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.