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: 7429823
• 负责人: STEVEN L JINKS
• 金额: $ 21.69万
• 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/7429823
• 关键词: Affect; Afferent Neurons; Alveolar; Anesthesia procedures; Anesthetics; Automobile Driving; Blood Pressure; Brain; Brain Stem; Class; Clinical; Data; Depressed mood; Depth; Development; Electrophysiology (science); Excitatory Amino Acid Antagonists; General anesthetic drugs; Glutamate Receptor; Glutamates; Glycine; Glycine Receptors; Halothane; Interneurons; Isoflurane; Lampreys; Locomotion; Mediating; Mental Depression; Midbrain structure; Monitor; Motor; Motor Activity; Motor Neurons; Motor output; Movement; N-Methylaspartate; NMDA receptor antagonist; Nerve; Nervous system structure; Neurons; Nociception; Numbers; Paralysed; Pathway interactions; Pattern; Physiologic Thermoregulation; Picrotoxin; Posterior Horn Cells; Preparation; Process; Range; Rattus; Research Personnel; Respiration; Sensory; Spinal; Spinal Cord; Stimulus; Swimming; Synaptic Transmission; System; Testing; Walking; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; amino 3 hydroxy 5 methylisoxazole 4 propionate; base; biceps brachii muscle; central pattern generator; clinically relevant; dorsal horn; extracellular; in vivo; inhibitory neuron; kainate; programs; receptor; relating to nervous system; research study; response; strychnine receptor

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取决于消除由超最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。然而，几乎没有关于介导这种运动的运动系统的麻醉作用的数据。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产生运动的脊髓运动和髓质神经元。该项目需要在大鼠体内和七鳃鳗离体脊髓制剂中进行单单位细胞外电生理学研究，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会直接破坏运动网络。我们假设麻醉剂在阻止运动所需的浓度下会阻止脊髓运动神经元对中脑运动区（MLR）的超最大伤害性刺激和电微刺激的反应。在七鳃鳗中，我们将使用尖峰触发的平均和逆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对抑制性神经元的抑制作用。目标 2：利用七鳃鳗的药理学方法，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 网络来发挥作用。我们假设 GABAA 和甘氨酸受体拮抗剂不会显着改变麻醉要求，并且挥发性麻醉剂对运动节律的影响与 I 组代谢型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。目标 3：在大鼠和七鳃鳗制剂中，我们将确定挥发性物质是否通过脊髓上的作用抑制下行运动驱动到脊髓。我们假设麻醉剂会抑制大鼠网状脊髓神经元对有害刺激和 MLR 微刺激的反应，而在七鳃鳗中，选择性地将麻醉剂输送到脑干会抑制网状脊髓神经元对 MLR 微刺激的反应和运动反应。全身麻醉剂是危险的，在临床浓度下会抑制血压、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以及在何处发挥作用的理解，有助于开发更安全的麻醉剂和临床实践。