Temporal Analysis of Memory Processes

内存过程的时间分析

• 批准号: 6951542
• 负责人: Joe Z Tsien
• 金额: $ 48.34万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6951542
• 关键词: Temporal; Analysis; Memory; Processes

DESCRIPTION (provided by applicant): The long-term goals of our research are to understand the molecular and cellular mechanisms of learning and memory in the brain. This application will focus on memory retrieval, a fundamental yet mysterious component believed to involve a rapid reconstructive process involving a new recapitulation of the learned information. Over the past several years, conditional gene knockout techniques have been shown to be increasingly valuable for molecular analysis of learning and memory processes. However, because these available techniques either lack temporal controls or only offer limited temporal resolutions, the molecular manipulations and analyses of memory retrieval process have not been rigorously attempted. This proposal will take advantage of our newly developed fourth-generation genetic technology that permits high time-resolution manipulations and analyses of the memory retrieval process. A comprehensive set of biochemical, genetic, and behavioral experiments will be conducted to demonstrate that memory retrieval, like other stages of memory process, can be selectively interfered through rapid manipulation of activity of a gene product known to play a crucial role in the regulation of synaptic plasticity. Another set of integrated analyses will be carried out to determine the possible cellular and neural mechanisms underlying the observed retrieval deficits. Finally, detailed electrophysiological analyses and additional genetic manipulations will be performed to further test the proposed hypothesis. Development and application of new genetic technology should increase researchers' ability to observe, manipulate, and discover the molecular and cellular processes underlying learning and memory in the mammalian brain. It is conceivable that such progress might eventually lead to new strategy for potential therapeutic interventions for the prevention and treatment of memory-related disorders.

描述（由申请人提供）：我们研究的长期目标是了解大脑学习和记忆的分子和细胞机制。该应用程序将集中于内存检索，这是一个基本而神秘的组成部分，涉及快速重建过程，涉及对学习信息的新概括。在过去的几年中，有条件的基因敲除技术被证明在学习和记忆过程的分子分析中越来越有价值。但是，由于这些可用技术要么缺乏时间控制，要么仅提供有限的时间分辨率，因此尚未严格尝试对记忆检索过程的分子操作和分析。该提案将利用我们新开发的第四代遗传技术，该技术允许对记忆检索过程进行高度分辨率的操纵和分析。将进行一组全面的生化，遗传和行为实验，以证明记忆检索与记忆过程的其他阶段一样，可以通过快速操纵已知在突触可变性调节中起着至关重要的基因产物的活性来选择性干预。将进行另一组综合分析，以确定观察到的检索缺陷的潜在细胞和神经机制。最后，将进行详细的电生理分析和其他遗传操作，以进一步检验拟议的假设。新遗传技术的开发和应用应提高研究人员观察，操纵和发现哺乳动物大脑中学习和记忆的分子和细胞过程的能力。可以想象，这种进展最终可能导致用于预防和治疗与记忆有关的疾病的潜在治疗干预措施的新策略。