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）：新的记忆通过巩固过程稳定下来，已知这取决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，这种观点最近受到了挑战，研究表明，当重新激活时，已建立的记忆变得不稳定，而且需要另一个阶段的蛋白质合成来维持。虽然这一过程被称为“再巩固”，但不知道它是否实际上是巩固的真实再现。关于记忆再巩固的潜在机制和具体功能知之甚少。这些知识不仅对理解记忆如何工作至关重要，而且还有助于开发基于创伤记忆（即创伤后应激障碍，恐惧症和抑郁症）的精神疾病治疗新策略和增加记忆强度的新方法。在这个项目中，我们建议使用恐惧条件为基础的任务（抑制性回避，IA）和分子研究进行比较多层次的分析的解剖和时间的分子要求的记忆巩固和再巩固。我们的目的是确定巩固和再巩固在多大程度上涉及相同的分子和大脑区域（电路）具有相似的时间动力学，并测试功能的作用和贡献的调制记忆再巩固。该项目的结果应提供重要信息，用于开发药物干预创伤性记忆引起的认知障碍（即创伤后应激障碍，恐惧症，成瘾和抑郁症）和记忆丧失的衰弱状况（如衰老和阿尔茨海默病）的新策略。