Mechanisms underlying memory stabilization

记忆稳定的机制

• 批准号: 7544500
• 负责人: CRISTINA M ALBERINI
• 金额: $ 38.14万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7544500
• 关键词: Aging; Alzheimer' s Disease; Amygdaloid structure; Anterior; Area; Belief; Brain; Brain region; Brain-Derived Neurotrophic Factor; CCAAT-Enhancer-Binding Proteins; Cognition Disorders; Development; Drug Addiction; Endocrine system; Gene Expression; Glucocorticoid Receptor; Glucocorticoids; Insulin-Like Growth Factor II; Intervention; Investigation; Knowledge; Laboratories; Learning; Measures; Mediating; Memory; Memory Disorders; Memory Loss; Molecular; Molecular Profiling; Muscle; Nucleus Accumbens; Pathway interactions; Phase; Phobic anxiety disorder; Post-Traumatic Stress Disorders; Process; Protein Biosynthesis; Protein Synthesis Inhibitors; Receptor Protein-Tyrosine Kinases; Regulation; Research Personnel; Resistance; Role; Screening procedure; Short-Term Memory; System; Testing; Time; Training; addiction; base; cholinergic; cingulate cortex; comparative; conditioned fear; depression; novel strategies; novel therapeutics; programs; research study

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.

描述（由申请人提供）：通过巩固过程稳定了新的记忆，该过程已知取决于蛋白质合成的临界阶段。综合记忆被普遍认为是稳定的，并且有弹性的破坏。然而，最近，这种信念受到了研究表明，在重新激活后，建立的记忆会不稳定，此外，还需要维持另一个蛋白质合成的阶段。尽管此过程被称为“重新固化”，但尚不清楚它是否是对整合的真实概括。关于基本机制和记忆重新整合的特定功能知之甚少。这些知识不仅对于了解记忆的工作原理至关重要，而且还将有助于发展基于创伤记忆（即创伤后应激障碍，恐惧症和抑郁症）的新型策略，以及增加记忆力的新方法。在这个项目中，我们建议使用基于恐惧条件的任务（抑制性避免，IA）和分子研究，以对记忆巩固和重新溶解的解剖学和时间分子需求进行比较的多级分析。我们的目的是确定合并和重新溶解的程度涉及具有相似时间动力学的相同分子和大脑区域（电路），并测试功能作用以及调制对记忆重新溶解的贡献。该项目的结果应为制定由创伤记忆（即PTSD，PHOBIA，成瘾和抑郁症）引起的认知障碍的药物治疗干预的新策略以及使记忆丧失的衰弱状况（例如在衰老和阿尔茨海默氏病中发生的记忆丧失）引起的重要信息。