Active Induction of Emergence from General Anesthesia

描述(由申请人提供)：培训计划：本建议描述了一项有指导的为期5年的研究培训计划，旨在培养麻醉机制方面的独立调查员。首席研究员是哈佛医学院(HMS)麻醉学助理教授和马萨诸塞州综合医院(MGH)麻醉师，具有麻醉药理学和电生理学背景。他的导师，埃默里·N·布朗博士，是HMS麻醉学沃伦·M·萨波尔教授，系计算神经科学教授。麻省理工学院(MIT)脑与认知科学教授，以及HMS和MIT健康科学与技术教授。有了导师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，足以制定独立的研究计划。他将在系里学习课程。他是麻省理工学院大脑和认知科学教授，他的研究培训将在麻省理工学院和加州大学圣地亚哥分校的实验室进行。这项提议的长期目标是使首席研究员为使用系统神经科学方法研究麻醉机制的成功的独立职业生涯做好准备。研究计划：越来越多的证据表明，大脑中的上升唤醒路径促进了全身麻醉(GA)的苏醒。阐明这些机制可能会改善对麻醉患者觉醒状态的药理学控制，更好地治疗突发性精神错乱，更好地检测术中意识，最终实现更安全、更有效的麻醉学实践。我们的初步数据表明，在稳态暴露于异氟醚期间，多巴胺能和胆碱能唤醒回路的药理激活会产生不同的唤醒状态，其特征是不同的行为和神经生理终点。这个项目的目的是阐明多巴胺能和胆碱能觉醒回路在促进GA出现方面的作用。结合药理学和脑微刺激技术，我们将探索GA主动诱导涌现的行为和神经生理学相关性。 与公共卫生相关：许多与全身麻醉(GA)苏醒相关的临床问题尚未得到解决，因为苏醒背后的神经机制尚未阐明。这个项目的目的是阐明多巴胺能和胆碱能觉醒回路在促进GA出现方面的作用。对这些机制的了解可能会导致临床护理的进步，包括控制患者觉醒状态的新方法，更好地治疗突发性精神错乱，以及改进的神经生理学监测仪，以优化麻醉剂量并保护患者免受术中意识。

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.