PROTEIN SYNTHESIS, CAMP RESPONSE ELEMENT BINDING PROTEIN

蛋白质合成，CAMP 反应元件结合蛋白

• 批准号: 6187628
• 负责人: STEPHAN G ANAGNOSTARAS
• 金额: $ 3.75万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6187628
• 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

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.

该项目的近期目标是研究蛋白质合成和CREB介导的转录在海马区空间表征的长期稳定中扮演什么角色(如果有的话)。这些地点表征被认为是动物用来解决空间学习问题的。同样，记忆的长期(但不是短期)稳定性依赖于蛋白质合成和CREB介导的转录。首先，将按照常规技术在小鼠身上检测大脑蛋白质合成抑制对海马区位置表征稳定性的影响。其次，已经开发了两种诱导CREB干扰的新技术，预计这两种技术都将导致海马区空间地图的长期而不是短期稳定性的缺陷。该建议的具体目的是检测[1]蛋白质合成抑制剂对野生型小鼠海马区细胞激发野稳定性的影响，[2]通过阻断多巴胺D1/D5受体抑制杂合子CREBalphaDelta+/-小鼠的cAMP/PKA通路，以及[3]在转基因小鼠中诱导CREB抑制物。最终目的是验证位置细胞维持的空间表征对长期空间记忆起中介作用的假设。这项研究将提高我们对海马体依赖记忆的细胞机制的理解。