How Brains Build Navigational Variables and Use them to Guide Behavior

项目摘要/摘要 我们的大脑为我们提供了一种我们在太空中所处位置的感觉。这种感觉的重要性是显而易见的，当我们 在空间上变得迷失方向，就像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年代的S(即当动物在空间的一个位置时，神经元处于活跃状态)，头部方向细胞在 20世纪80年代的S(即动物面对一个罗盘方向时活跃的神经元)，以及早期的网格细胞 2000年的S(即，当动物在空间中的位置网格中时，活跃的神经元)。根本的下一步 在我们对空间认知的理解中，将描述引起这种情况的电路级别的相互作用 了解生理活动模式并了解这些信号最终如何影响导航行为。 我们希望利用果蝇的先进遗传、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，它解释了 导航信号被建立起来。第二，我们希望改进飞行执行的任务，而我们从 他们的大脑，这将使我们能够分离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种记忆形成的分子、细胞和电路机制。 形成并引导行为。这项工作应该允许我们更严格地将分子因素联系起来，通过它们的 对细胞和电路的影响，对它们在空间认知中的作用。我们的发现最终应该有助于 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到一辆车， 以及如何处理这种能力受损的神经状况，如阿尔茨海默氏症 疾病。

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.