Temporal Analysis of Memory Processes

描述(申请人提供)：我们研究的长期目标是了解大脑中学习和记忆的分子和细胞机制。这个应用程序将专注于记忆提取，这是一个基本而神秘的组成部分，据信涉及一个快速的重建过程，涉及对学习信息的新概括。在过去的几年里，条件性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。然而，由于这些现有的技术要么缺乏时间控制，要么只能提供有限的时间分辨率，因此对记忆提取过程的分子操纵和分析还没有被严格尝试。这项提议将利用我们新开发的第四代基因技术，允许对记忆提取过程进行高时间分辨率的操作和分析。将进行一系列全面的生化、遗传学和行为学实验，以证明记忆恢复，就像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塑性调节中发挥关键作用的基因产物的活性来选择性地干扰。将进行另一套综合分析，以确定导致观察到的提取缺陷的可能的细胞和神经机制。最后，将进行详细的电生理分析和额外的遗传操作，以进一步验证所提出的假设。新基因技术的发展和应用将提高研究人员观察、操作和发现哺乳动物大脑学习和记忆潜在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新的战略，潜在的治疗干预措施，以预防和治疗记忆相关的疾病。

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.