GABAA AND NMDA RECEPTORS: ELECTROPHYSIOLOGIC STUDIES

GABAA 和 NMDA 受体：电生理学研究

• 批准号: 6807224
• 负责人: ROBERT A PEARCE
• 金额: $ 21.59万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6807224
• 关键词: GABA receptor; NMDA receptors; anesthetics; anticonvulsants; behavior test; electrophysiology; gene mutation; genetically modified animals; hippocampus; inhalation anesthesia; ketamine; laboratory mouse; learning; long term potentiation; memory; memory disorders; midazolam; neural plasticity; neural transmission; neuropharmacology; pharmacokinetics; protein structure function; receptor expression; sedative /hypnotic; tissue /cell preparation

Inhaled anesthetics impair learning and memory by mechanisms that remain unknown. GABAA and NMDA receptors are considered prime candidates because a wide variety of inhaled and injected anesthetics alter the activity of these receptors, and because some injected agents that impair learning and memory (e.g., midazolam and ketamine) act specifically through these receptors. Our proposal tests the hypothesis that inhaled anesthetics suppress memory formation by altering GABAA and or NMDA receptor function. We will test this hypothesis by comparing the effects of inhaled anesthetics and specific modulators of GABAA or NMDA receptors on synaptic transmission, synaptic plasticity, and memory. Our subjects will be wild-type mice and mice harboring point mutations that render specific GABAA or NMDA receptors insensitive to inhaled agents. Because the hippocampus is a well-characterized cortical structure and is implicated in the formation of explicit memories, experiments will focus on receptors that are expressed in the hippocampus, on hippocampal synapses, and on hippocampal-dependent learning.

吸入麻醉剂会通过尚不清楚的机制损害学习和记忆。 GABAA 和 NMDA 受体被认为是主要候选受体，因为多种吸入和注射麻醉剂会改变这些受体的活性，并且因为一些损害学习和记忆的注射药物（例如咪达唑仑和氯胺酮）专门通过这些受体发挥作用。我们的提案测试了吸入麻醉剂通过改变 GABAA 和/或 NMDA 受体功能来抑制记忆形成的假设。我们将通过比较吸入麻醉剂和 GABAA 或 NMDA 受体的特定调节剂对突触传递、突触可塑性和记忆的影响来检验这一假设。我们的受试者将是野生型小鼠和携带点突变的小鼠，这些突变使特定的 GABAA 或 NMDA 受体对吸入剂不敏感。由于海马体是一种特征明确的皮质结构，并且与外显记忆的形成有关，因此实验将重点关注海马体中表达的受体、海马突触和海马依赖性学习。