Biology of memory

记忆生物学

• 批准号: 10595455
• 负责人: Ronald L Davis
• 金额: $ 119.76万
• 依托单位: UNIVERSITY OF 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 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10595455
• 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.

项目摘要 该建议是针对长期且灵活的研究计划，旨在获得对生物学的关键见解 学习和记忆。尽管灵活性在其设计中是固有的，但新颖的观察结果已经进行了 研究过程可以并且将不会延迟进行，该计划以三个主要线路为基础 研究：（1）分子，细胞和系统神经科学是主动过程的基础 忘记，（2）大脑在其之间组织不同类型的嗅觉记忆的逻辑 成分神经元，以及（3）蛋白质编码和microRNA基因的鉴定和表征 功能以抑制内存形成的过程。主动遗忘的组成部分源于最近的 识别信号系统，该信号系统消除了先前形成的记忆，并由内部调节 唤醒和睡眠状态，以及外部感觉刺激。这代表了一个未研究的区域 记忆形成的神经科学，并为分子生物学提供了巨大的发现机会 和系统的神经科学。第二部分建立在创新发现的基础上 允许可视化细胞记忆迹线 - 由于 学习 - 这为记忆如何在大脑中组织的逻辑提供了一个窗口。此组件 作为一个例子，对比，大脑如何组织嗅觉记忆与有益的相关性 提示和与厌恶提示相关的人，并深入研究了基本机制。这 第三个成分源自最近提供了许多新基因的遗传筛选，这两者都蛋白 编码和microRNA编码，在被抑制时会增强内存，从而表示新内存 抑制基因。提出的行为，功能性细胞成像和分子遗传实验 将以不同的临时记忆形式剖析这些基因的作用：短，中间和长 术语内存；以及内存形成的不同操作阶段：获取，内存稳定性或 忘记。结果将为大脑用来限制记忆的约束提供前所未有的观点 形成。鉴于有据可查的认知问题，这项研究具有丰富的医学意义 与众多神经和精神疾病有关。