Mechanism Underlying Memory Stabilization

描述（由申请人提供）：保持健康的认知功能，其中记忆是最重要的一个，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认知功能的逐渐下降，称为轻度认知障碍。此外，患阿尔茨海默病、记忆力减退和痴呆症的风险随着年龄的增长而增加。因此，随着平均寿命的持续延长，最大限度地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，以制定预防或逆转它们的策略。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，如果通过另一个被称为记忆再巩固的过程重新恢复和稳定，记忆就会再次变得不稳定。使用上下文恐惧条件反射类型的记忆在大鼠中，我们最近发现，生长因子胰岛素样生长因子II（IGF-II）作为一个强大的记忆增强剂时，在巩固或再巩固阶段。此外，使用抑制性回避（IA），我们已经发现，提取依赖的再巩固促进记忆强化和防止遗忘。这些发现表明，有可能确定提取后机制，这些机制可用作开发新疗法的靶点，以促进认知和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，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。它将研究提取诱导的记忆强化和预防遗忘的电路和分子机制。最后，它将研究如何记忆检索和IGF-II可以在老化延迟或逆转记忆障碍。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.