PROTEIN SYNTHESIS, CAMP RESPONSE ELEMENT BINDING PROTEIN

蛋白质合成，CAMP 反应元件结合蛋白

基本信息

批准号：
6019898
负责人：
STEPHAN G ANAGNOSTARAS
金额：
$ 3.17万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-12-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/6019898
关键词：
behavior test brain electrical activity brain metabolism cAMP response element binding protein dopamine receptor genetic transcription genetically modified animals hippocampus injection /infusion laboratory mouse learning long term memory microelectrodes protein biosynthesis short term memory space perception tamoxifen

项目摘要

The proximal objective of the project is to examine what role, if any, protein synthesis and CREB-mediated transcription play in the long-term stabilization of spatial representations in the hippocampus. These place representations are believed to be used by animals to solve spatial learning problems. Likewise, the long-term (but not short-term) stability of memory depends on protein synthesis and CREB-mediated transcription. First, the effect of cerebral protein synthesis inhibition on the stability of hippocampal place representations will be examined in mice according to a conventional technique. Second, two novel techniques for inducing CREB disruption have been developed and are both expected to produce deficits in long-term, but not short-term stability of the hippocampal spatial map. The specific aims of the proposal are to examine the effects on hippocampal place cell firing field stability of [1] protein synthesis inhibiton in wildtype mice, [2] inhibition of the cAMP/PKA pathway, via dopamine D1/D5 receptor blockade, in heterozygous CREBalphadelta+/- mice, and [3] the induction of a CREB repressor in transgenic mice. The ultimate objective is to test the hypothesis that spatial representations maintained by place cells mediate long-term spatial memory. This research will improve our understanding of the cellular mechanisms of hippocampus-dependent memory.

该项目的近端目标是检查在海马中空间表示的长期稳定中，蛋白质合成和CREB介导的转录发挥。这些地方表示被动物用来解决空间学习问题。同样，记忆的长期（但不是短期）稳定性取决于蛋白质的合成和CREB介导的转录。首先，将根据常规技术在小鼠中检查脑蛋白合成抑制对海马位置表示的稳定性的影响。其次，已经开发了两种用于诱导CREB破坏的新技术，并且有望长期产生缺陷，但不会对海马空间图的短期稳定性产生缺陷。该提案的具体目的是检查对野生型小鼠中[1]蛋白质合成抑制剂的海马放电场稳定性的影响，[2]通过多巴胺D1/D5受体阻断，在杂合子中，通过多巴胺D1/D5受体阻断来抑制营地/PKA途径。克雷巴德尔塔尔+/ - 小鼠，[3]转基因小鼠诱导CREB抑制剂。最终目标是检验以下假设：通过位置细胞维持的空间表示介导了长期的空间记忆。这项研究将提高我们对海马依赖性记忆的细胞机制的理解。