Biology of memory

项目摘要 该提案是一个长期和灵活的研究计划，旨在获得生物学的关键见解 学习和记忆。虽然灵活性是其设计所固有的， 研究的进程能够而且将毫不拖延地进行下去，该计划以三条主要路线为基础 （1）分子，细胞和系统神经科学，这些科学是活动过程的基础。 遗忘，（2）大脑组织不同类型的嗅觉记忆的逻辑， 组成神经元，和（3）蛋白质编码和microRNA基因的鉴定和表征， 具有抑制记忆形成过程的功能。主动遗忘成分源于最近的 一种信号系统的识别方法，该系统删除了先前形成的存储器，并由内部调制器进行调制。 唤醒和睡眠状态，以及外部感官刺激。这是一个未研究的领域， 神经科学的记忆形成，并提供了巨大的机会，发现在分子生物学 和系统神经科学。第二个组成部分是建立在创新发现的基础上， 允许细胞记忆痕迹的可视化-神经元响应特性的变化， 学习-这为了解记忆在大脑中是如何组织的逻辑提供了一个窗口。此组件 对比，作为一个例子，大脑是如何组织嗅觉记忆的，这些记忆是与奖励相关联的。 线索和那些与厌恶线索相关的学习，并深入研究其内在机制。的 第三种成分来自最近的基因筛选，这些筛选提供了大量的新基因， 编码和microRNA编码，它们在被抑制时增强记忆，从而代表新的记忆。 抑制基因拟议的行为、功能细胞成像和分子遗传学实验 将剖析这些基因在不同时间形式的记忆中的作用：短期记忆、中期记忆和长期记忆。 术语记忆;以及记忆形成的不同操作阶段：获取，记忆稳定性，或 遗忘研究结果将为我们提供一个前所未有的视角，来了解大脑用来限制记忆的限制因素 阵有丰富的医学重要性，这项研究给予充分记载的问题，认知 与许多神经和精神疾病有关。

Project Summary This proposal is for a long-term and flexible research program designed to obtain key insights into the biology of learning and memory. Although flexibility is inherent in its design, such that novel observations made over the course of the research can and will be pursued without delay, the program is grounded in three major lines of research: (1) the molecular, cellular, and systems neuroscience that underlie the process of active forgetting, (2) the logic by which the brain organizes different types of olfactory memories among its component neurons, and (3) the identification and characterization of protein-coding and microRNA genes that function to suppress the process of memory formation. The active forgetting component stems from the recent identification of a signaling system that removes previously formed memories and is modulated by internal states of arousal and sleep, and by external sensory stimulation. This represents an unstudied area in the neuroscience of memory formation and offers tremendous opportunities for discovery in the molecular biology and systems neuroscience of the process. The second component is founded on innovative discoveries that allow the visualization of cellular memory traces – changes in the response properties of neurons due to learning – that offer a window into the logic behind how memories are organized in the brain. This component contrasts, as one example, how the brain organizes olfactory memories learned in association with a rewarding cue and those learned in association with an aversive cue, and delves into the underlying mechanisms. The third component derives from recent genetic screens that have provided a plethora of new genes, both protein- coding and microRNA-coding, which enhance memory when suppressed, thus representing new memory suppressor genes. The proposed behavioral, functional cellular imaging, and molecular genetic experiments will dissect the roles for these genes in different temporal forms of memory: short-, intermediate-, and long- term memory; as well as different operational phases of memory formation: acquisition, memory stability, or forgetting. The results will offer an unprecedented view of the constraints the brain uses to limit memory formation. There is a rich medical importance to this research given the well-documented problems of cognition associated with numerous neurological and psychiatric disorders.