How Brains Build Navigational Variables and Use them to Guide Behavior

大脑如何构建导航变量并利用它们来指导行为

• 批准号: 10665382
• 负责人: GABY MAIMON
• 金额: $ 59.33万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2031-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665382
• 关键词: Alzheimer' s Disease; Anatomy; Animals; Automobile Driving; Behavior; Behavioral; Brain; Cell Separation; Cells; Cognition; Confusion; Dementia; Deterioration; Disorientation; Drosophila genus; Face; Genetic; Goals; Head; Home; Human; Impairment; Individual; Link; Location; Memory; Molecular; Neurologic; Neurons; Pattern; Physiological; Short-Term Memory; Signal Transduction; Societies; Subway; Work; fly; improved; member; neural circuit; novel therapeutic intervention; tool; way finding

Project Summary / Abstract Our brain provides us with a sense of where we are in space. The importance of this sense is clear when we become spatially disoriented, like when one is confused about one’s orientation after exiting a subway station. Central to the understanding of how brains give rise to spatial cognition has been the discovery of place cells in the 1970’s (i.e., neurons that are active when animals are in one location in space), head-direction cells in the 1980’s (i.e., neurons that are active when animals face one compass direction), and grid cells in the early 2000’s (i.e., neurons that are active when animals are in a grid of locations in space). A fundamental next step in our understanding of spatial cognition would be to describe the circuit-level interactions that give rise to such physiological activity patterns and to understand how such signals ultimately influence navigational behavior. We wish to leverage the advanced genetic, behavioral, anatomical and physiological tools in Drosophila, to achieve three broad goals. First, we wish to rigorously characterize neural circuits that explain how navigational signals are built. Second, we wish to improve the tasks that flies perform while we record from their brain, which will allow us to isolate cells and circuits required for the formation of spatial working memories. Third, we aim to reveal molecular, cellular and circuit mechanisms by which such memories are formed and guide behavior. This work should allow us to more rigorously link molecular factors, through their effects on cells and circuits, to their function in spatial-cognition. Our discoveries should ultimately help to inform how humans perform navigational tasks like driving home from work or finding a car in a parking lot, alongside how to approach neurological conditions in which such abilities are impaired, like in Alzheimer’s disease.

项目总结/摘要 我们的大脑让我们感觉到自己在空间中的位置。这种感觉的重要性是显而易见的，当我们 在空间上迷失方向，就像当一个人在离开地铁站后对自己的方向感到困惑。 理解大脑如何产生空间认知的核心是发现了大脑中的位置细胞。 20世纪70年代（即，当动物在空间中的一个位置时活跃的神经元）， 1980年代（即，当动物面向一个指南针方向时活跃的神经元），以及早期的网格细胞 2000年（即，当动物处于空间中的位置网格中时，神经元是活跃的）。一个基本的下一步 在我们对空间认知的理解中， 生理活动模式，并了解这些信号如何最终影响导航行为。 我们希望利用果蝇先进的遗传、行为、解剖和生理工具， 实现三大目标。首先，我们希望严格描述神经回路，解释如何 导航信号已经建立。第二，我们希望改善苍蝇执行的任务，而我们记录从 他们的大脑，这将使我们能够分离出形成空间工作所需的细胞和电路 回忆第三，我们的目标是揭示这些记忆的分子，细胞和电路机制。 形成并引导行为。这项工作应该使我们能够更严格地联系分子因素，通过他们的 对细胞和电路的影响，对它们在空间认知中的功能的影响。我们的发现最终将有助于 告知人类如何执行导航任务，如下班开车回家或在停车场找车， 以及如何处理这种能力受损的神经系统疾病，如阿尔茨海默氏症， 疾病