Biology of memory

记忆生物学

• 批准号: 10536019
• 负责人: Ronald L Davis
• 金额: $ 2.29万
• 依托单位: SCRIPPS FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2022-04-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10536019
• 关键词: Area; Arousal; Behavioral; Biology; Brain; Code; Cognition; Cues; Diagnostic; Genes; Genetic Screening; Human; Impairment; Knowledge; Lead; Learning; Logic; Mediating; Medical; Memory; Mental disorders; MicroRNAs; Molecular; Molecular Biology; Molecular Genetics; Neurons; Neurosciences; Phase; Process; Property; Proteins; Research; Rewards; Role; Sensory; Signal Transduction; Sleep; Suppressor Genes; System; Visualization; brain disorder therapy; cellular imaging; design; experimental study; flexibility; forgetting; gene function; imaging genetics; innovation; insight; long term memory; memory process; nervous system disorder; neuron component; novel; programs; response; stem

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.

项目概要 该提案是一项长期且灵活的研究计划，旨在获得对生物学的关键见解 尽管其设计具有固有的灵活性，但新的观察结果会被忽略。 研究进程可以而且将会立即进行，该计划基于三个主要方向 研究范围：（1）构成主动活动过程基础的分子、细胞和系统神经科学 遗忘，（2）大脑在其记忆中组织不同类型嗅觉记忆的逻辑 组成神经元，以及 (3) 蛋白质编码和 microRNA 基因的鉴定和表征 抑制记忆形成过程的功能源于最近的记忆形成过程。 识别信号系统，删除先前形成的记忆并由内部调制 唤醒和睡眠状态以及外部感官刺激这代表了一个未经研究的领域。 记忆形成的神经科学，为分子生物学的发现提供了巨大的机会 该过程的第二部分是基于创新发现。 允许细胞记忆痕迹的可视化——神经元响应特性的变化 学习——为了解大脑中记忆如何组织背后的逻辑提供了一个窗口。 举个例子，对比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知识，并深入研究潜在的机制。 第三个成分来自最近的基因筛选，提供了大量新基因，包括蛋白质- 编码和 microRNA 编码，在受到抑制时增强记忆，从而代表新的记忆 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记忆形式中的作用：短记忆、中记忆和长记忆 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 研究结果将为大脑用来限制记忆的限制提供一个前所未有的视角。 鉴于认知问题已有充分记录，这项研究具有丰富的医学重要性。 与许多神经和精神疾病有关。