Temporal Analysis of Memory Processes

描述（由申请人提供）：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。这个应用程序将集中在记忆检索，一个基本的但神秘的组成部分，相信涉及一个快速的重建过程，涉及一个新的重演的学习信息。在过去的几年中，条件基因敲除技术已被证明是越来越有价值的学习和记忆过程的分子分析。然而，由于这些现有的技术要么缺乏时间控制或只提供有限的时间分辨率，记忆提取过程的分子操作和分析还没有严格的尝试。这项建议将利用我们新开发的第四代遗传技术，允许高时间分辨率的操作和分析的记忆检索过程。一套全面的生化，遗传和行为实验将进行证明，记忆检索，像记忆过程的其他阶段，可以选择性地通过快速操纵的基因产物的活性干扰已知发挥关键作用的调节突触可塑性。将进行另一组综合分析，以确定所观察到的检索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，以进一步测试所提出的假设。新的遗传技术的发展和应用将提高研究人员观察、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，这种进展可能最终导致潜在的治疗干预的新策略，用于预防和治疗记忆相关疾病。

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.