Project 4: Mathematical Modeling Studies of Anesthetic Action

项目4：麻醉作用的模型研究 全麻是一种令人着迷的人造神经生理现象，已经发展起来。 多年来的经验证明，能够安全和人性化地执行手术和非手术程序。 具体地说，它是一种由药物引起的状态，包括意识丧失、健忘、止痛和静止， 以及生理稳定性。在美国，每天有6万名患者接受全身麻醉 麻醉剂如何在大脑中产生麻醉状态的机制还不是很好。 明白了。最近在表征麻醉药的分子位置方面取得了重大进展 目标。然而，对特定分子靶标的作用如何导致行为状态还不太清楚。 解决这一问题需要系统神经科学方法来定义药物在特定情况下的作用 分子靶点和神经回路导致全身麻醉的行为状态。在该计划项目中 题为《麻醉的集成系统神经科学研究》，我们将开发一个集成系统 神经科学项目包括人类、非人灵长类、啮齿动物和四个模型研究 麻醉药：GABAA类药物异丙酚和七氟醚，α-2肾上腺素能激动剂右旋美托咪定； 以及NMDA受体拮抗剂氯胺酮。该计划项目还将包括数据分析核心， 它将为数据分析提供辅助，并对统计方法进行研究。具体目标 是为了了解麻醉剂对特定分子靶点和神经回路的作用是如何产生的 振荡动力学(脑电节律、LFP的变化和神经放电活动)可能是主要的 麻醉剂产生不同的唤醒状态(镇静、幻觉、 无意识)。建模研究的目标将是开发详细的电路级描述 每种麻醉剂每种大脑状态背后的神经生理机制。建模将提供 系统地组织和集成所有三个实验项目中的信息 这样，我们就可以对麻醉剂的作用机制做出准确的陈述。作为一项研究， 继续下去，建模将使我们能够做出可以通过实验检验的预测。除了……之外 这些研究为麻醉状态的系统神经科学提供了新的见解，也将提供 关于大脑唤醒回路的神经生理学的基本定量知识将是 与其他神经心理问题的研究相关，如昏迷、疼痛、睡眠和抑郁。

PROJECT 4: MODELING STUDIES OF ANESTHETIC ACTION General anesthesia is a fascinating man-made, neurophysiological phenomenon that has been developed empirically over many years to enable safe and humane performance of surgical and non-surgical procedures. Specifically it is a drug-induced condition consisting of unconsciousness, amnesia, analgesia and immobility, along with physiological stability. General anesthesia is administered daily to 60,000 patients in the United States, the mechanisms for how anesthetics act in the brain to create the states of anesthesia are not well understood. Significant progress has been made recently in characterizing the molecular sites that anesthetics target. However, how actions at specific molecular targets lead to the behavioral states is less well understood. Addressing this issue requires a systems neuroscience approach to define how actions of the drugs at specific molecular targets and neural circuits lead to a behavioral state of general anesthesia. In this program project entitled, Integrated Systems Neuroscience Studies of Anesthesia, we will develop an integrated systems neuroscience program consisting of human, non-human primate, rodent and modeling studies of four anesthetics: the GABAA agents, propofol and sevoflurane; the alpha-2 adrenergic agonist, dexmedetomidine; and the NMDA receptor antagonist, ketamine. The program project will also include a DATA ANALYSIS CORE, which will provide assistant with data analysis and conduct research on statistical methods. The Specific Aims are to understand how the actions of the anesthetics at specific molecular targets and neural circuits produce the oscillatory dynamics (EEG rhythms, changes in LFPs and neural spiking activity) that are likely a primary common mechanism through which anesthetics create altered states of arousal (sedation, hallucination, unconsciousness). The goal of the modeling research will be to develop detailed, circuit-level descriptions of the neurophysiological mechanisms underlying each brain state of each anesthetic. The modeling will provide a systematic way to organize and integrate information across all of the three experimental projects and thereby, allow us to develop precise statements about anesthetic mechanisms of action. As the research proceeds, the modeling will enable us to make predictions that can be tested with experiments. In addition to providing new insights into the systems neuroscience of anesthetic states, these studies will also provide fundamental new quantitative knowledge about the neurophysiology of the brain's arousal circuits that will be relevant to studies of other neuropsychological problems such as coma, pain, sleep and depression.