AGRIN AND INTEGRIN EXPRESSION IN LEARNING AND LTP

学习和 LTP 中的 AGRIN 和整合素表达

基本信息

批准号：
6346169
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
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-08-01 至 2001-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6346169
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

项目摘要

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中观察到突触形态的变化，因此已知有助于突触接触的稳定性的蛋白质特别感兴趣地了解记忆功能。总体目标是研究Agrin和整联蛋白的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。农业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起重要作用。在学习和长期增强中都观察到形态学变化和/或突触发生。初步研究发现，在学习空间导航任务时，动物的大脑再次诱导mRNA表达。我们也有证据表明，阿格林mRNA用海马长期增强表达。海马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至少显示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），另一种需要激活这需要激活Opiodagric受体。在通往面积CA3区域的横向穿孔路径，齿状回的侧面穿孔路径以及苔藓纤维到CA3区域的横向穿孔路径中发现了阿片类药物。因此，基因表达可以通过NMDA和阿片受体的激活来调节。在长期潜能期间，Agrin和整联蛋白mRNA表达将在穿孔途径的回流和穿孔途径CA3途径中使用清醒的大鼠进行研究。这些途径表达了NMDA和阿片受体依赖性的长期增强。具体目标1将研究长期增强过程中Agrin和整联蛋白的时间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Agrin或整联蛋白mRNA表达。特定的目标2将调查莫里斯水迷宫任务的空间学习期间阿格林的时间过程。纳洛酮和选择性阿片类受体和NMDA受体拮抗剂将用于研究在这种学习形式的过程中，阿片类药物或NMDA受体的激活是否参与了Agrin或整合素mRNA的表达。这些研究还将研究是否使用阿片类药物或NMDA受体拮抗剂施用学习障碍，这与Agrin和整合素mRNA表达的阻断相似。