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介导的转录在海马空间表征的长期稳定中发挥的作用。 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（而不是短期）稳定性取决于蛋白质合成和CREB介导的转录。 首先，将根据常规技术在小鼠中检查脑蛋白质合成抑制对海马位置表征稳定性的影响。 第二，已经开发了两种新的诱导CREB中断的技术，并且预期这两种技术都将在海马空间图的长期而非短期稳定性中产生缺陷。 该提案的具体目的是检查[1]野生型小鼠中蛋白质合成抑制剂对海马位置细胞放电场稳定性的影响，[2]通过多巴胺D1/D5受体阻断杂合CREB adelta +/-小鼠中cAMP/PKA通路的抑制，以及[3]转基因小鼠中CREB阻遏物的诱导。 最终的目标是测试的假设，空间表征维持的位置细胞介导的长期空间记忆。 本研究将有助于我们更好地理解海马依赖性记忆的细胞机制。