Mechanism Underlying Memory Stabilization

描述（由申请人提供）：保持健康的认知功能是心理健康研究的主要目标之一，其中记忆是最重要的一项。衰老、疾病、压力和伤害都会导致认知和记忆障碍。据估计，随着年龄的增长，多达三分之一的成年人会经历认知功能的逐渐下降，这被称为轻度认知障碍。此外，阿尔茨海默病、记忆丧失和痴呆的风险随着年龄的增长而增加。因此，随着平均寿命的不断延长，减少或防止认知和记忆丧失是非常重要的。因此，了解记忆形成、持久和储存的生理学，识别与记忆障碍相关的分子机制和目标，以制定预防或逆转记忆障碍的策略，是势在必行的。新学到的信息在有限的时间内处于不稳定状态，并通过一个稳定的过程成为长期记忆，这个过程被称为记忆巩固。一旦稳定，如果通过另一个被称为记忆再巩固的过程来检索和重新稳定，记忆就会再次变得不稳定。利用大鼠的情境恐惧条件反射记忆类型，我们最近发现，在巩固或再巩固阶段给药时，生长因子胰岛素样生长因子II （IGF-II）是一种有效的记忆增强剂。此外，使用抑制性回避（IA），我们发现检索依赖的再巩固促进记忆加强和防止遗忘。这些发现表明，有可能确定后检索机制，可以作为开发新疗法的目标，以促进认知和减轻与年龄相关的记忆衰退。利用IA和大鼠食物偏好的社会传递，本研究将测试提取依赖性igf - ii诱导的记忆增强的分子机制和脑回路。它将研究检索诱导记忆加强和预防遗忘的电路和分子机制。最后，它将研究记忆检索和IGF-II如何在衰老中使用，以延迟或逆转记忆损伤。这些研究结果将促进我们对大鼠记忆增强和衰老相关认知障碍的神经机制的认识。

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.