Project 4: Mathematical Modeling Studies of Anesthetic Action

项目4：麻醉作用的数学模型研究

• 批准号: 9209580
• 负责人: NANCY KOPELL
• 金额: $ 27.34万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-10 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9209580
• 关键词: Absence of pain sensation; Address; Adrenergic Agonists; Affect; Amnesia; Anesthesia procedures; Anesthetics; Arousal; Behavioral; Brain; Brain Stem; Brain region; Cell Nucleus; Coma; Data Analyses; Dexmedetomidine; Dose; Drug effect disorder; Electroencephalography; Frequencies; General Anesthesia; Glutamates; Goals; Hallucinations; Human; Interneurons; Investigation; Ketamine; Kinetics; Knowledge; Lead; Mediating; Mental Depression; Modeling; Molecular; Molecular Target; NMDA receptor antagonist; Neurons; Neuropsychology; Neurosciences; Operative Surgical Procedures; Pain; Parietal; Parietal Lobe; Patients; Performance; Pharmaceutical Preparations; Pharmacology; Phase; Physiological; Propofol; Research; Rodent Model; Sedation procedure; Sleep; Statistical Methods; Study models; System; Testing; Thalamic structure; Unconscious State; United States; experimental study; fascinate; frontal lobe; gamma-Aminobutyric Acid; hippocampal pyramidal neuron; inhibitory neuron; insight; locus ceruleus structure; man; mathematical model; molecular site; neural circuit; neurophysiology; nonhuman primate; noradrenergic; parabrachial nucleus; programs; relating to nervous system; sevoflurane

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.

项目4：麻醉作用的建模研究