Mechanisms underlying memory stabilization

描述(申请人提供)：一种新的记忆是通过巩固过程来稳定的，这是已知的依赖于蛋白质合成的关键阶段。人们普遍认为，巩固的记忆是稳定的，对破坏具有弹性。然而，这一信念最近受到了挑战，因为研究表明，已建立的记忆在重新激活时变得不稳定，而且需要另一个蛋白质合成阶段来维持。尽管这个过程被称为“再整合”，但我们不知道它实际上是否真的是整合的重演。人们对记忆再巩固的潜在机制和具体功能知之甚少。这一知识不仅对理解记忆是如何工作的至关重要，而且还将有助于开发治疗基于创伤记忆的精神疾病(即创伤后应激障碍、恐惧症和抑郁症)的新策略，以及增强记忆力的新方法。在这个项目中，我们建议使用基于恐惧的任务(抑制性回避，IA)和分子研究来对记忆巩固和再巩固的解剖学和时间分子需求进行相对多水平的分析。我们的目标是确定巩固和再巩固在多大程度上涉及具有相似时间动力学的相同分子和大脑区域(回路)，并测试调制在记忆再巩固中的功能作用和贡献。该项目的结果将为制定新的策略，对创伤记忆(即创伤后应激障碍、恐惧症、成瘾和抑郁)和衰弱记忆丧失引起的认知障碍(如老年和阿尔茨海默病)进行药物治疗干预提供重要信息。

DESCRIPTION (provided by applicant): A new memory is stabilized through a process of consolidation, which is known to depend on a critical phase of protein synthesis. Consolidated memories are widely believed to be stable and resilient to disruption. This belief, however, has been recently challenged by studies showing that established memories become labile when reactivated and, furthermore, require another phase of protein synthesis to be maintained. Although this process has been termed "re-consolidation", it is not known whether it is, in fact, a true recapitulation of consolidation. Very little is known about the underlying mechanisms and the specific functions of memory reconsolidation. This knowledge is not only essential for the understanding of how memory works, but it will also contribute to the development of novel strategies for treating psychiatric conditions based on traumatic memories (i.e. post-traumatic stress disorders, phobias and depression) and novel approaches for increasing memory strength. In this project, we propose to use a fear-conditioned-based task (inhibitory avoidance, IA) and molecular investigations to carry out a comparative multiple level analysis of the anatomical and temporal molecular requirements of memory consolidation and reconsolidation. Our Aims are to determine to what extent both consolidation and reconsolidation involve the same molecules and brain areas (circuits) with similar temporal dynamics and to test the functional roles and the contribution of modulation on memory reconsolidation. The results of this project should provide important information for developing new strategies for the pharmacotherapeutic intervention of cognitive disorders caused by traumatic memories (i.e. PTSD, phobias, addiction and depression) and debilitating conditions of memory loss such as those occurring in aging and Alzheimer's Disease.