Gene Expression in Long-Term Memory

保持和促进健康的认知功能，其中记忆是最重要的功能之一 心理健康研究的主要目标之一。疾病、压力、伤害和衰老会导致 认知和记忆障碍。据估计，多达三分之一的成年人将经历 随着年龄的增长，认知功能逐渐下降，称为轻度认知障碍。此外， 许多疾病，如阿尔茨海默氏症、自闭症、智力低下，都与 记忆力受损。因此，最大限度地减少或预防认知和记忆损伤是非常重要的 心理健康的重要目标。实现这一目标的主要方法是理解 记忆形成、持久和储存的生理机制及识别分子 可用于增强记忆的机制和靶点，不仅用于增强正常 不仅用于开发可防止或逆转记忆丧失的策略。使用RAT和 在小鼠模型中，我们已经确定生长因子胰岛素样生长因子2(IGF-2)是一种有效的 健康状态下的记忆和认知增强剂。使用这两种记忆损伤的模型 发育障碍和衰老，我们发现IGF-2可以显著逆转记忆丧失。我们的 最近5年的研究也开始阐明IGF-2的一些作用机制 促进记忆增强和逆转记忆缺陷。其中一种机制是作为 自噬/溶酶体降解系统，细胞功能的关键调节因子。此外， 提供大脑皮层区域记忆形成和增强机制的研究 缓慢发展的学习诱导的变化不同于已知的突触可塑性的证据。 该提案旨在继续这些机械性的调查，以便：1--确定 自噬/溶酶体降解在记忆巩固和IGF-2介导的记忆中的作用 加强及其关键目标机制；2--确定身份和管理 训练后在皮质区域出现的新生物机制对 记忆巩固和增强；以及3-确定髓鞘形成在长期记忆中的作用 队形。这些研究的结果将极大地促进我们对大脑的了解 可塑性机制，可能是实现记忆增强和治疗认知障碍的靶点。

Maintaining and promoting healthy cognitive functions, of which memory is a most important one, is one of the major goals of mental health research. Diseases, stress, injury and aging 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, a number of diseases such as Alzheimer's disease, autism, mental retardation are associated with memory impairments. Thus, minimizing or preventing cognitive and memory impairments is a very important goal in mental health. A principal approach toward this goal is to understand the physiological mechanisms of memory formation, persistence and storage and identify molecular mechanisms and targets that can be used to enhance memory, not only for potentiating normal functions but also for developing strategies that may prevent or reverse memory loss. Using rat and mouse models, we have identified the growth factor insulin like growth factor 2 (IGF-2) as a potent memory and cognitive enhancer in healthy conditions. Using models of memory impairment in both developmental disorders and aging we found that IGF-2 significantly reverses memory losses. Our studies of the last 5 years also started elucidating some of the action mechanisms by which IGF-2 promotes memory enhancement and reverse memory deficits. One of these mechanisms emerged as the autophagy/lysosomal degradation system, a key regulator of cell functions. Furthermore, investigations of mechanisms of memory formation and enhancement in cortical regions provided evidence for slow-developing learning-induced changes distinct from the known synaptic plasticity. This proposal aims at continuing these mechanistic investigations in order to: 1- Determine the role of autophagy/lysosomal degradation in memory consolidation and IGF-2-mediated memory enhancement, as well as their critical target mechanisms; 2- Determine identity and regulation of novel biological mechanisms occurring in cortical areas following training that are critical for memory consolidation and enhancement; and 3- Determine the role of myelination in long-term memory formation. Results from these studies should significantly advance our knowledge of brain plasticity mechanisms, which may be targeted to achieve memory enhancement and to treat cognitive disorders.