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）：一般麻醉药的固定效力取决于消融多种有害的有害性刺激所带来的多种段，节奏的运动运动所需的最低浓度。但是，几乎没有关于介导该运动的运动系统上麻醉作用的数据。拟议的研究旨在了解挥发性麻醉药（卤硫烷和异氟烷）如何影响特定的运动产生脊柱运动和髓质神经元。项目需要在大鼠体内和七lamp鼠孤立的脊髓制剂中进行单个单元外电生理学，并采用药理学方法应用于七lamp虫。 AIM 1：我们将确定挥发性代理是否会直接破坏运动网络。我们假设麻醉剂阻断脊柱运动神经元对超大性有害刺激和中脑运动区域（MLR）的电化微刺激的反应，以阻止运动所需的浓度。在Lamprey中，我们将使用尖峰触发的平均和抗肿瘤激活来确定兴奋性和抑制性中心模式产生（CpG）神经元。我们假设麻醉药比抑制性神经元更能抑制兴奋性CpG神经元。 AIM 2：使用七lamp鼠的药理学方法，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网络来起作用。我们假设GABAA和甘氨酸受体拮抗剂并不能显着改变麻醉的需求，并且挥发性麻醉会影响与对I组甲苯性谷氨酸受体拮抗剂的影响一致的运动节律，但与AMPA和NMDA受体抗体的影响不符，但与AMPA和NMDA受体的影响不符。 AIM 3：在大鼠和七lamp虫的制剂中，我们将确定挥发性剂是否通过上脊柱上的作用将运动降低到脊髓的降低。我们假设大鼠网状髓质神经元对有害刺激以及对MLR微刺激的麻醉反应降低了，并且在七含lamp，选择性地递送麻醉剂到脑干上，向脑干降低了网状神经脊髓的反应和运动对MLR微刺激的反应。一般麻醉剂是危险的，在临床浓度下降低了血压，呼吸和温度调节。这些项目的结果将增加我们对麻醉在神经系统中的作用和何处的理解，从而有助于开发更安全的麻醉和临床实践。