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Volatile Anesthetic Action in Vertebrate Locomotor Systems

脊椎动物运动系统中的挥发性麻醉作用

基本信息

批准号：
7858193
负责人：
STEVEN L JINKS
金额：
$ 21.47万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-06-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7858193
关键词：
Affect Afferent Neurons Alveolar Anesthesia procedures Anesthetics Automobile Driving Blood Pressure Brain Brain Stem Clinical Data Depressed mood Development Electrophysiology (science)Excitatory Amino Acid Antagonists General anesthetic drugs Glutamate Receptor Glutamates Glycine Glycine Receptors Halothane Interneurons Isoflurane Lampreys Locomotion Mediating Mental Depression Metabotropic Glutamate Receptors Midbrain structure Monitor Motor Motor Activity Motor Neurons Motor output Movement N-Methylaspartate NMDA receptor antagonist Nerve Nervous system structure Neurons Nociception Paralysed Pathway interactions Pattern Physiologic Thermoregulation Picrotoxin Posterior Horn Cells Preparation Process Rattus Research Personnel Respiration Sensory Spinal Spinal Cord Stimulus Swimming Synaptic Transmission System Testing Walking base biceps brachii muscle central pattern generator clinical practice clinically relevant dorsal horn electrical microstimulation extracellular in vivo inhibitory neuron kainate microstimulation programs receptor relating to nervous system research study response strychnine receptor

项目摘要

DESCRIPTION (provided by applicant): The immobilizing potencies of general anesthetics are determined by the minimum concentration necessary to ablate multisegmental, rhythmic locomotor-type movements elicited by supramaximal noxious stimuli. However, almost no data exist regarding anesthetic action on locomotor systems that mediate this movement. The proposed studies aim to understand how volatile anesthetics (halothane and isoflurane) affect specific classes of movement-generating spinal locomotor and medullary neurons. Projects entail single-unit extracellular electrophysiology in both rat in vivo and lamprey isolated spinal cord preparations, with pharmacological approaches applied to lamprey. Aim 1: We will determine if volatile agents direcly disrupt locomotor networks. We hypothesize that anesthetics block responses of spinal locomotor neurons to both supramaximal noxious stimuli and electrical microstimulation of the mesencephalic locomotor region (MLR) at concentrations necessary to block movement. In lamprey, we will identify excitatory and inhibitory central pattern generating (CPG) neurons using spike-triggered averaging and antidromic activation. We hypothesize that anesthetics suppress excitatory CPG neurons more than inhibitory neurons. Aim 2: Using pharmacological approaches in lamprey, we will determine if volatile anesthetics act largely by direct suppression of excitatory CPG networks. We hypothesize that GABAA and glycine receptor antagonists do not significantly change anesthetic requirements, and that volatile anesthetics affect the locomotor rhythm consistent with effects on group I metabotropic glutamate receptor antagonists, but not consistent with effects of AMPA and NMDA receptor antagonists. Aim 3: In both rat and lamprey preparations, we will determine if volatile agents depress descending locomotor drive to the spinal cord by a supraspinal action. We hypothesize that anesthetics depress responses of rat reticulospinal medullary neurons to noxious stimuli as well as to MLR microstimulation, and that in the lamprey, selective delivery of anesthetics to the brainstem depresses reticulospinal neuronal responses and motor responses to MLR microstimulation. General anesthetics are dangerous, depressing blood pressure, respiration, and thermoregulation at clinical concentrations. Results from these projects will increase our understanding of how and where anesthetics act in the nervous system, contributing to the development of safer anesthetics and clinical practices.

说明(申请人提供)：全身麻醉药的固定效力取决于消融超最大伤害性刺激所引起的多节段、节律性运动型运动所需的最低浓度。然而，几乎没有关于麻醉对调节这种运动的运动系统的作用的数据。这项拟议的研究旨在了解挥发性麻醉剂(氟烷和异氟烷)如何影响特定类别的运动产生脊髓运动和延髓神经元。该项目需要在大鼠体内和七鳃鳗分离的脊髓制备中进行单个单位的细胞外电生理学，并将药理学方法应用于七鳃鳗。目标1：我们将确定挥发性物质是否直接扰乱运动网络。我们假设麻醉剂阻断脊髓运动神经元对超最大伤害性刺激和中脑运动区(MLR)电微刺激的反应，所需浓度达到阻断运动所需的浓度。在七鳃鳗中，我们将使用尖峰触发的平均和反向激活来识别兴奋性和抑制性中枢模式生成(CPG)神经元。我们假设麻醉剂对兴奋性CPG神经元的抑制作用大于抑制性神经元。目的2：在七鳃鳗中使用药理学方法，我们将确定挥发性麻醉剂是否主要通过直接抑制兴奋性CPG网络起作用。我们假设GABAA和甘氨酸受体拮抗剂不会显著改变麻醉要求，而挥发性麻醉剂影响的运动节律与I组代谢性谷氨酸受体拮抗剂的作用一致，但与AMPA和NMDA受体拮抗剂的作用不一致。目的3：在大鼠和七鳃鳗中，我们将确定挥发性物质是否通过脊椎上的作用抑制脊髓的下行运动驱动。我们假设麻醉剂抑制了大鼠延髓网状神经元对伤害性刺激和MLR微刺激的反应，而在七鳃鳗中，选择性地向脑干注射麻醉药抑制了网状脊髓神经元对MLR微刺激的反应和运动反应。全身麻醉药是危险的，在临床浓度下会降低血压、呼吸和体温调节。这些项目的结果将增加我们对麻醉剂在神经系统中如何起作用以及在哪里起作用的理解，有助于开发更安全的麻醉剂和临床实践。