Volatile Anesthetic Action in Vertebrate Locomotor Systems

脊椎动物运动系统中的挥发性麻醉作用

• 批准号: 7131336
• 负责人: STEVEN L JINKS
• 金额: $ 24.76万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7131336
• 关键词: Agnatha; GABA receptor; anesthetics; brain regulatory center; chordate locomotion; electrostimulus; glycine receptors; halothane; inhalation anesthesia; isoflurane; laboratory rat; medulla oblongata; motor neurons; neural information processing; neural inhibition; neural transmission; pharmacokinetics; spinal cord; spinal nerves

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.

描述（由申请人提供）：全身麻醉剂的固定效力由消除超大伤害性刺激引起的多节段、节律性运动型运动所需的最低浓度决定。然而，几乎没有数据存在关于麻醉作用的运动系统，介导这种运动。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。项目需要在大鼠体内和七鳃鳗分离的脊髓制备的单单位细胞外电生理学，与应用于七鳃鳗的药理学方法。目的1：我们将确定挥发性药物是否直接破坏运动网络。我们假设，麻醉剂块脊髓运动神经元的反应，以超大伤害性刺激和电微刺激的中脑运动区（MLR）在必要的浓度，以阻止运动。在七鳃鳗，我们将确定兴奋性和抑制性中央模式产生（CPG）神经元使用尖峰触发的平均和逆向激活。我们假设麻醉剂抑制兴奋性CPG神经元多于抑制性神经元。目标二：使用药理学方法在七鳃鳗，我们将确定挥发性麻醉剂的行为主要是通过直接抑制兴奋性CPG网络。我们假设GABAA和甘氨酸受体拮抗剂不会显著改变麻醉需求，挥发性麻醉剂影响运动节律，与对I组代谢型谷氨酸受体拮抗剂的影响一致，但与AMPA和NMDA受体拮抗剂的影响不一致。目标3：在大鼠和七鳃鳗准备，我们将确定是否挥发性药物抑制下行运动驱动脊髓的脊髓上的行动。我们假设麻醉剂抑制大鼠网状脊髓髓神经元对伤害性刺激以及对MLR微刺激的反应，并且在七鳃鳗中，选择性地向脑干递送麻醉剂抑制网状脊髓神经元对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作用的方式和位置的理解，有助于开发更安全的麻醉剂和临床实践。