AGRIN AND INTEGRIN EXPRESSION IN LEARNING AND LTP

学习和 LTP 中的 AGRIN 和整合素表达

• 批准号: 6256919
• 负责人: EDWIN J BAREA-RODRIGUEZ
• 金额: $ 14.87万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-09-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6256919
• 关键词: NMDA receptors; agrin; gene expression; hippocampus; in situ hybridization; integrins; laboratory rat; learning; long term potentiation; messenger RNA; neural plasticity; neuroanatomy; opioid receptor; polymerase chain reaction; protein structure function; space perception; synapses; western blottings

Since changes in synaptic morphology are observed in learning and long- term potentiation, proteins known to contribute to the stability of synaptic contacts are of particular interest to understand memory functions. The overall goal is to investigate mRNA expression of agrin and integrins, and the factors that may mediate their expression in the rat hippocampus during long-term potentiation and spatial learning. Agrins and integrins are extracellular matrix proteins that may play an important role in synaptogenesis and the modification of existing synapses. Both morphological changes and/or synaptogenesis have been observed in learning and long-term potentiation. Preliminary studies find that again mRNA expression is induced in the brain of animals during learning a spatial navigational task. We have evidence also that agrin mRNA is expressed with hippocampal long-term potentiation. The hippocampus displays t least two forms of synaptic plasticity, one that requires the activation of the glutaminergic receptor displays at least two forms of synaptic plasticity, one that requires the activation of the glutaminergic receptor N-Methyl-D-Aspartate (NMDA) and another that requires the activation of opiodergic receptors. Opioids are found in the lateral perforant path to area CA3, the lateral perforant path to dentate gyrus, and the mossy fiber to area CA3. Thus gene expression may be modulated by the activation of NMDA and opioid receptors. Agrin and integrin mRNA expression during long-term potential will be investigated in the perforant path-dentate gyrus and the perforant path-CA3 pathways using awake freely-moving rats. These pathways expressed NMDA and opioid- receptor dependent long-term potentiation. Specific Aim 1 will investigate temporal mRNA expression of agrin and integrins during long-term potentiation. Naloxone and selective opioid or NMDA receptor antagonists will be used to investigate if the activation of opioid or NMDA receptors is involved in agrin or integrins mRNA expression. Specific Aim 2 will investigate the time course induction of agrin during spatial learning of the Morris water maze task. Naloxone and selective opioid receptor and NMDA receptor antagonists will be used to investigate if the activation of opioid or NMDA receptors is involved in agrin or integrins mRNA expression during this form of learning. These studies will investigate also if the impairment in learning observed with the administration of opioid or NMDA receptor antagonists parallel the blockade of agrin and integrin mRNA expression.

由于在学习和长期增强过程中观察到突触形态的变化，因此已知有助于突触接触稳定性的蛋白质对于理解记忆功能特别有意义。总体目标是研究集聚蛋白和整合素的 mRNA 表达，以及在长期增强和空间学习过程中可能介导其在大鼠海马中表达的因素。集聚蛋白和整合素是细胞外基质蛋白，可能在突触发生和现有突触的修饰中发挥重要作用。在学习和长期增强中观察到形态变化和/或突触发生。 初步研究发现，在学习空间导航任务期间，动物大脑中再次诱导 mRNA 表达。我们还有证据表明集聚蛋白 mRNA 的表达具有海马长时程增强作用。海马体表现出至少两种形式的突触可塑性，一种需要激活谷氨酰胺能受体表现出至少两种形式的突触可塑性，一种需要激活谷氨酰胺能受体 N-甲基-D-天冬氨酸（NMDA），另一种需要激活谷氨酰胺能受体 N-甲基-D-天冬氨酸（NMDA），另一种需要激活谷氨酰胺能受体这需要激活阿片受体。阿片类药物存在于通往 CA3 区的外侧穿通路径、通往齿状回的外侧穿通路径以及通往 CA3 区的苔藓纤维中。因此，基因表达可以通过 NMDA 和阿片受体的激活来调节。将使用清醒的自由活动大鼠在穿通路径-齿状回和穿通路径-CA3 通路中研究长期电位期间的集聚蛋白和整合素 mRNA 表达。这些途径表达 NMDA 和阿片受体依赖性长期增强作用。具体目标 1 将研究长期增强过程中集聚蛋白和整合素的时间 mRNA 表达。纳洛酮和选择性阿片类药物或 NMDA 受体拮抗剂将用于研究阿片类药物或 NMDA 受体的激活是否参与集聚蛋白或整合素 mRNA 表达。具体目标 2 将研究莫里斯水迷宫任务空间学习期间集聚蛋白的时间过程诱导。纳洛酮和选择性阿片受体和 NMDA 受体拮抗剂将用于研究阿片或 NMDA 受体的激活是否参与这种形式的学习过程中集聚蛋白或整合素 mRNA 的表达。这些研究还将调查阿片类药物或 NMDA 受体拮抗剂给药所观察到的学习障碍是否与集聚蛋白和整合素 mRNA 表达的阻断同时发生。