Mechanism Underlying Memory Stabilization

描述(申请人提供)：保持健康的认知功能，其中记忆是最重要的之一，是心理健康研究的主要目标之一。衰老、疾病、压力和损伤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将经历被称为轻度认知障碍的认知功能逐渐下降。此外，随着年龄的增长，患阿尔茨海默病、S病、记忆力丧失和痴呆症的风险也会增加。因此，随着平均寿命的持续延长，尽量减少或防止认知和记忆丧失是非常重要的。因此，必须了解记忆形成、持久性和储存的生理学，并确定与记忆损伤相关的分子机制和靶点，以便制定预防或逆转记忆损伤的策略。新学到的信息在有限的时间内处于不稳定状态，并通过一个被称为记忆巩固的稳定过程成为长期记忆。一旦稳定下来，如果被找回，记忆可能会再次变得不稳定，并通过另一个称为记忆重新巩固的过程重新稳定。利用大鼠的情景恐惧条件记忆，我们最近发现，生长因子胰岛素样生长因子II(IGF-II)在巩固或再巩固阶段使用时，可以作为一种有效的记忆增强剂。此外，利用抑制回避(IA)，我们发现依赖提取的再巩固促进了记忆的加强和防止遗忘。这些发现表明，有可能确定提取后机制，作为目标，开发新的治疗方法，促进认知并缓解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，这项建议将测试提取依赖的IGF-II诱导的记忆增强的分子机制和大脑回路。它将研究提取诱导记忆增强和防止遗忘的电路和分子机制。最后，它将调查记忆提取和IGF-II如何在衰老过程中用于延缓或逆转记忆损伤。这些研究的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了解。 公共卫生相关性：利用我们正在进行的以大鼠为动物模型的项目的最新发现，该项目继续旨在确定成年动物记忆增强的机制和回路，以及在预防或挽救记忆衰退方面的作用。这些研究的结果可能会导致发现预防或逆转记忆损伤的新疗法。预防或挽救认知和记忆丧失是心理健康研究中最重要的目标。

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. PUBLIC HEALTH RELEVANCE: Capitalizing on recent findings from our ongoing project using the rat as an animal model, this project continuation aims at identifying the mechanisms and circuitry of memory enhancement in adult animals and in preventing or rescuing memory decay. The results of these studies may lead to the identification of new therapies that prevent or reverse memory impairments. Preventing or rescuing cognitive and memory loss is a most important goal in mental health research.