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介导的转录在海马体空间表征的长期稳定中所起的作用（如果有的话）。这些位置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（而非短期）稳定性取决于蛋白质合成和creb介导的转录。首先，根据常规方法，在小鼠中检测脑蛋白合成抑制对海马位置表征稳定性的影响。其次，已经开发了两种诱导CREB中断的新技术，这两种技术都有望导致海马空间图的长期而非短期稳定性的缺陷。本研究的具体目的是研究野生型小鼠[1]蛋白合成抑制、杂合子CREBalphadelta+/-小鼠[2]通过多巴胺D1/D5受体阻断对cAMP/PKA通路的抑制以及转基因小鼠[3]诱导CREB抑制因子对海马位置细胞放电场稳定性的影响。最终目的是验证由位置细胞维持的空间表征介导长期空间记忆的假设。这项研究将提高我们对海马体依赖性记忆的细胞机制的理解。