Anesthetic Effects on Thalamic Synaptic Transmission

麻醉对丘脑突触传递的影响

• 批准号: 6732289
• 负责人: PETER A GOLDSTEIN
• 金额: $ 30.16万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6732289
• 关键词: GABA receptor; action potentials; anesthetics; central nervous system depressants; drug interactions; electrodes; electrophysiology; infrared microscopy; isoflurane; laboratory mouse; membrane potentials; neural inhibition; neural transmission; neurons; organ culture; sensory mechanism; thalamus; voltage /patch clamp

DESCRIPTION (provided by applicant): The mechanisms by which a diverse group of pharmacological agents produce anesthesia remain uncertain. A potentially important region within the central nervous system (CNS) for contributing to the anesthetized state is the thalamus; it is a critical relay site for sensory information, and two specific nuclei, the ventrobasal nucleus and the reticular nucleus, are considered to be essential structures in the generation of consciousness and sleep. Since anesthetics depress consciousness and induce "sleep," it is important to understand how anesthetics alter synaptic transmission and cell physiology in these two regions. Inhibitory synaptic transmission helps regulate thalamic function, and the GABA-A receptor is the primary receptor for mediating fast inhibitory synaptic transmission within the CNS. The focus of this proposal is to explore how two different anesthetic agents, the volatile anesthetic - isoflurane, and the intravenous anesthetic - propofol, modulate inhibitory synaptic transmission and neuronal activity in the ventrobasal nucleus and reticular nucleus. Aim 1 - What are the effects of propofol on synaptic transmission and membrane excitability in the thalamus? The hypothesis to be tested is that propofol will potentiate synaptic inhibition and depress neuronal activity to a greater extent in VB neurons than in RTN neurons. Aim 2 - What are the effects of isoflurane on synaptic transmission and membrane excitability in the thalamus? The hypothesis to be tested is that isoflurane will potentiate synaptic inhibition and depress neuronal activity to a greater extent in VB neurons than in RTN neurons. Aim 3 - How do propofol and isoflurane affect the ability of the RTN to regulate action potential firing in the VB? The hypothesis to be tested is that both agents will facilitate RTN-induced inhibition of action potential firing in VB neurons. By better understanding how anesthetic agents interact with specific subunits of the GABA-A receptor in different regions of the brain, it may be possible to design more selective, and therefore safer, anesthetics.

描述（由申请人提供）： 多样化的药理剂产生麻醉的机制仍然不确定。丘脑是中枢神经系统（CNS）内的潜在重要区域（CNS）。它是一个关键的感官信息继电器位点，两个特定的核，腹膜核和网状核被认为是意识和睡眠产生的必不可少的结构。由于麻醉药降低意识并引起“睡眠”，因此了解麻醉药如何改变这两个区域的突触传播和细胞生理学很重要。抑制性突触传播有助于调节丘脑功能，而GABA-A受体是介导CNS内快速抑制性突触传递的主要受体。该提案的重点是探索两种不同的麻醉剂，挥发性麻醉 - 异氟醚以及静脉麻醉 - 丙泊酚 - 丙泊松，调节腹膜核和网状核中的抑制性突触传播和神经元活性。目标1-丙泊酚对丘脑中突触传播和膜兴奋性有什么影响？要检验的假设是，与RTN神经元相比，在VB神经元中，丙泊将增强突触抑制并降低神经元活性。 AIM 2-异氟烷对丘脑中突触传播和膜兴奋性有什么影响？要测试的假设是，异氟烷将增强突触抑制作用并在VB神经元中比RTN神经元更大程度地降低神经元活性。 AIM 3-丙泊酚和异氟烷如何影响RTN调节VB中动作电势射击的能力？要检验的假设是，两种药物都将促进RTN诱导的VB神经元中的动作电势发射的抑制作用。通过更好地了解麻醉剂如何与大脑不同区域中GABA-A受体的特定亚基相互作用，可以设计更具选择性，更安全的麻醉剂。