MOLECULAR BIOLOGY OF MEMORY

记忆的分子生物学

• 批准号: 3084288
• 负责人: STEVEN Scott SCHREIBER
• 金额: $ 9.12万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-06-01 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3084288
• 关键词: animal age group; cell differentiation; gene expression; genetic transcription; hippocampus; histochemistry /cytochemistry; immunochemistry; in situ hybridization; laboratory rabbit; laboratory rat; long term memory; long term potentiation; messenger RNA; molecular psychobiology; neurophysiology; northern blottings; protein biosynthesis; protooncogene; tissue /cell culture

The long term objectives of this application will be to further the understanding of the molecular basis of learning and memory and to apply this knowledge to studies of diseases, such as Alzheimer's Disease. It is widely accepted that the acquisition of long-term memory is a process which depends upon protein synthesis. Hence, it has been postulated that this process is linked to the expression of one or more genes which may be involved in long-term adaptive modifications within the cell. Studies of invertebrate behavior have disclosed that simple forms of learning are characterized by molecular and ionic events with result in changes in synaptic function. Such changes also occur with long-term potentiation (LTP) which has been proposed as a model of neural plasticity and long- term memory processing in the mammalian nervous system. The acquisition of long-term memory bears a striking resemblance to processes which occur during cell growth and differentiation. Therefore, this application will focus on defining the molecular events underlying LTP by examining the level of expression of a proto-oncogene, c-fos. Protooncogenes, such as c-fos, are thought to play a regulatory role in cell growth and differentiation. Hence, it is possible that the heightened neuronal activity associated with LTP is related to c-for induction. We will use c-fos cDNA as a probe and perform Northern blot and in situ hybridization studies to evaluate the level of expression and localize the signal of c- fos message in the rat and rabbit hippocampus during LTP. Immunohistochemical techniques will be conducted to localize Fos protein. In this way, a gene or genes which are important in memory mechanisms and an anatomic substrate of LTP may be identified. Changes in levels of c- fos expression with age will also be studied. It is hoped that these studies will contribute to further understanding of the molecular basis of normal and abnormal cognitive function.

本申请的长期目标将是进一步 了解学习和记忆的分子基础，并将其应用于 这些知识可以应用于疾病的研究，比如阿尔茨海默氏症。 它 长期记忆的获得是一个过程， 这取决于蛋白质的合成。因此，有人假设， 这一过程与一种或多种基因的表达有关， 参与细胞内的长期适应性修改。研究 无脊椎动物行为的研究揭示了简单的学习形式 其特征在于分子和离子事件， 突触功能这种变化也发生在长时程增强中 (LTP)它被认为是神经可塑性和长期- 哺乳动物神经系统中的术语记忆处理。收购 长时记忆的过程与 在细胞生长和分化过程中。因此，本申请将 重点是通过检查LTP的分子事件来定义LTP的分子事件。 原癌基因c-fos的表达水平。原癌基因，如 c-fos被认为在细胞生长中起调节作用， 分化 因此，有可能是神经元增强 与LTP相关的活性与c-for诱导有关。我们将使用 以c-fos cDNA为探针，进行北方杂交和原位杂交 研究以评估表达水平和定位c- 大鼠和家兔海马LTP过程中fos信息的变化 免疫组化技术将进行定位Fos蛋白。 这样，在记忆机制中重要的一个或多个基因， 可以确定LTP的解剖学基础。C水平的变化- 还将研究随年龄的Fos表达。希望这些 研究将有助于进一步了解分子基础 正常和异常的认知功能。