Mechanism Underlying Memory Stabilization

记忆稳定的机制

• 批准号: 8418715
• 负责人: CRISTINA M ALBERINI
• 金额: $ 60.05万
• 依托单位: NEW YORK UNIVERSITY
• 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 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8418715
• 关键词: Adult; Age; Age-associated memory impairment; Aging; Alzheimer' s disease risk; Animal Model; Behavioral; Brain; Cognition; Data; Defect; Dementia; Disease; Enhancers; Food Preferences; Gene Expression; Genetic Transcription; Goals; Grant; Growth Factor; Impaired cognition; Injury; Insulin-Like Growth Factor II; Investigation; Knowledge; Lead; Learning; Learning Disabilities; Longevity; Memory; Memory Loss; Memory impairment; Mental Health; Mental disorders; Molecular; Nature; Pathology; Phase; Physiology; Positioning Attribute; Post-Traumatic Stress Disorders; Prevention; Process; Rattus; Research; Retrieval; Stress; Technology; Testing; Therapeutic; Time; Translations; Trauma; addiction; age related; aged; base; clinical application; cognitive function; conditioned fear; experience; forgetting; long term memory; mature animal; memory retention; memory retrieval; mild cognitive impairment; neuromechanism; novel; pre-clinical; prevent; research study; social; tool; transmission process

DESCRIPTION (provided by applicant): Maintaining healthy cognitive functions, of which memory is a most important one, is one of the major goals of mental health research. Aging, diseases, stress and injury can lead to cognitive and memory impairments. It is estimated that up to one third of adults will experience a gradual decline in cognitive function known as mild cognitive impairment as they age. Furthermore, risk for Alzheimer<s disease, memory loss and dementia increases with increasing age. Thus, minimizing or preventing cognitive and memory loss is very important as the average life span continues to lengthen. It is therefore imperative to understand the physiology of memory formation, persistence and storage and identify molecular mechanisms and targets that are associated with memory impairments in order to develop strategies that will prevent or reverse them. Newly learned information is in a labile state for a limited time and becomes a long-term memory through a process of stabilization that is known as memory consolidation. Once stable, memory can become labile again if retrieved and re-stabilizes through another process known as memory reconsolidation. Using contextual fear conditioning types of memory in rats, we have recently found that the growth factor insulin like growth factor II (IGF-II) acts as a potent memory enhancer when administered during the consolidation or reconsolidation phases. Furthermore, using inhibitory avoidance (IA), we have found that retrieval-dependent reconsolidation promotes memory strengthening and prevents forgetting. These findings suggest that it is possible to identify post-retrieval mechanisms that can be used as targets to develop new therapies that promote cognition and alleviate age- related memory decline. Using IA and social transmission of food preference in rats, this proposal will test the molecular mechanisms and brain circuitry of the retrieval-dependent IGF-II-induced memory enhancement. It will investigate circuitry and molecular mechanisms of retrieval-induced memory strengthening and prevention of forgetting. Finally, it will investigate how memory retrieval and IGF-II can be used in aging to delay or reverse memory impairments. Results from these studies will advance our knowledge of neural mechanisms underlying memory enhancement and aging-related cognitive impairment in rats.

描述（由申请人提供）：维持健康的认知功能，其中最重要的是心理健康研究的主要目标之一。衰老，疾病，压力和伤害会导致认知和记忆力障碍。据估计，随着年龄的增长，多达三分之一的成年人的认知功能被称为轻度认知障碍。此外，随着年龄的增长，阿尔茨海默氏病，记忆力丧失和痴呆症的风险增加。因此，随着平均寿命继续延长，最小化或预防认知和记忆丧失非常重要。因此，必须了解记忆形成，持久性和存储的生理学，并确定与记忆障碍相关的分子机制和目标，以制定可以防止或反向它们的策略。新学习的信息在有限的时间内处于不稳定状态，并且通过称为记忆巩固的稳定过程成为长期记忆。一旦稳定，如果检索并通过另一个称为内存重新稳定的过程重新稳定，记忆将再次变得不稳定。我们最近发现，在巩固或重新固定阶段进行施用时，使用大鼠中记忆的记忆类型，例如生长因子胰岛素II（IGF-II）像生长因子II（IGF-II）充当有效的内存增强子。此外，使用抑制性避免（IA），我们发现检索依赖性重新溶解会促进记忆的增强并防止遗忘。这些发现表明，可以识别可用作靶向靶向的靶标，以促进认知并减轻与年龄相关的记忆下降。使用IA和大鼠食物偏好的社交传播，该建议将测试依赖于检索依赖性IGF-II诱导的记忆增强的分子机制和脑回路。它将研究检索诱导的记忆加强和预防遗忘的电路和分子机制。最后，它将调查如何将内存检索和IGF-II用于衰老来延迟或逆转内存障碍。这些研究的结果将提高我们对大鼠内存增强和与衰老相关的认知障碍的神经机制的了解。