Active Induction of Emergence from General Anesthesia

描述（由申请人提供）：培训计划：该提案描述了一项为期5年的指导研究培训计划，旨在培养一名麻醉机制方面的独立研究者。首席研究员是哈佛医学院（HMS）麻醉学助理教授和麻省总医院（MGH）的麻醉师，具有麻醉药理学和电生理学的背景。他的导师Emery N. Brown博士是HMS的Warren M. Zapol麻醉教授、麻省理工学院（MIT）脑与认知科学系的计算神经科学教授、HMS和MIT的健康科学与技术教授。有了指导临床科学家研究职业发展奖，首席研究员将获得系统神经科学方面的新知识和技能，足以发展一个独立的研究项目。他将在麻省理工学院脑与认知科学系学习，他的研究训练将在麻省理工学院MGH和加州大学圣地亚哥分校的实验室进行。这项建议的长期目标是准备首席研究员成功的独立职业生涯研究麻醉机制使用系统神经科学的方法。研究计划：越来越多的证据表明，大脑中上升的唤醒通路促进全身麻醉（GA）的苏醒。阐明这些机制可能会改善麻醉患者觉醒状态的药理学控制，更好地治疗突发性谵妄，更好地监测术中意识，最终实现更安全、更有效的麻醉实践。我们的初步数据表明，在稳态暴露于异氟醚时，多巴胺能和胆碱能唤醒回路的药理激活产生了不同的唤醒状态，其特征是不同的行为和神经生理终点。本项目的目的是阐明多巴胺能和胆碱能唤醒回路在促进GA出现中的作用。利用药物和脑微刺激技术的结合，我们将探索主动诱导GA出现的行为和神经生理相关因素。

DESCRIPTION (provided by applicant): Training Plan: This proposal describes a mentored 5-year research training program for the development of an independent investigator in anesthetic mechanisms. The Principal Investigator is an Assistant Professor of Anaesthesia at Harvard Medical School (HMS) and a faculty anesthesiologist at Massachusetts General Hospital (MGH), with a background in anesthetic pharmacology and electrophysiology. His mentor, Dr. Emery N. Brown, is Warren M. Zapol Professor of Anaesthesia at HMS, Professor of Computational Neuroscience in the Dept. of Brain and Cognitive Sciences at the Massachusetts Institute of Technology (MIT), and Professor of Health Sciences and Technology at HMS and MIT. With the Mentored Clinical Scientist Research Career Development Award, the Principal Investigator will acquire new knowledge and skills in systems neuroscience sufficient to develop an independent research program. He will take courses in the Dept. of Brain and Cognitive Sciences at MIT, and his research training will take place in laboratories at MGH, MIT, and the University of California, San Diego. The long-term objective of this proposal is to prepare the Principal Investigator for a successful independent career studying anesthetic mechanisms using a systems neuroscience approach. Research Plan: Accumulating evidence suggests that ascending arousal pathways in the brain promote emergence from general anesthesia (GA). Elucidating these mechanisms may lead to improved pharmacological control over the arousal states of anesthetized patients, better treatments for emergence delirium, better neurophysiological monitors to detect intraoperative awareness, and ultimately a safer and more efficient practice of anesthesiology. Our preliminary data suggest that pharmacological activation of dopaminergic and cholinergic arousal circuits during steady-state exposure to isoflurane produce distinct arousal states that are characterized by different behavioral and neurophysiological endpoints. The goal of this project is to elucidate the roles of dopaminergic and cholinergic arousal circuits in promoting emergence from GA. Using a combination of pharmacological and brain microstimulation techniques, we will probe the behavioral and neurophysiological correlates of actively induced emergence from GA. PUBLIC HEALTH RELEVANCE: Many of the clinical problems related to emergence from general anesthesia (GA) have not been solved because the neural mechanisms underlying emergence have not been elucidated. The goal of this project is to elucidate the roles of dopaminergic and cholinergic arousal circuits in promoting emergence from GA. Knowledge of these mechanisms may lead to advances in clinical care including novel methods to control the arousal states of patients, better treatments for emergence delirium, and improved neurophysiological monitors that optimize anesthetic dosing and protect patients from intraoperative awareness.