Biology of memory

项目摘要 这项建议是为了一个长期和灵活的研究计划，旨在获得对生物学的关键见解 学习和记忆的能力。尽管灵活性是其设计所固有的，因此新的观察结果 研究的进程可以而且将毫不拖延地进行，该计划以三条主要路线为基础 研究方面：(1)作为活动过程基础的分子、细胞和系统神经科学 遗忘，(2)大脑组织不同类型的嗅觉记忆的逻辑 组成神经元，以及(3)蛋白质编码基因和microRNA基因的鉴定和特征 抑制记忆形成过程的功能。活跃的遗忘成分源于最近的 一种信令系统的标识，它删除以前形成的存储器，并由内部调制 唤醒和睡眠状态，以及外部感官刺激。这代表着一个未被研究的领域 记忆形成的神经科学，并为分子生物学的发现提供了巨大的机会 以及这一过程的系统神经科学。第二部分建立在创新发现的基础上， 允许可视化细胞记忆痕迹-神经元响应特性的变化 学习--它提供了一个窗口，让我们了解记忆在大脑中是如何组织起来的。此组件 作为一个例子，对比了大脑如何组织与奖励相关的嗅觉记忆 线索和那些与厌恶线索相关的习得线索，并深入探讨潜在的机制。这个 第三部分来自最近的基因筛查，这些筛查提供了过多的新基因，既有蛋白质，也有 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、中期和长期- 术语记忆；以及记忆形成的不同操作阶段：习得、记忆稳定性或 忘记了。这一结果将提供一个前所未有的视角，了解大脑用来限制记忆的限制 队形。鉴于认知问题的详细记录，这项研究具有丰富的医学意义。 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.