Neural circuits for spatial navigation

项目概要/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特定位置时活跃的神经元），头部方向 20世纪80年代的细胞（即，当动物面对一个特定的罗盘方向时，神经元是活跃的）， 2000年代早期的细胞（即，当动物处于空间中的位置网格中时，神经元是活跃的）。一 这些细胞的一个显著特征是，即使动物在完全封闭的环境中航行，它们的放电模式也会持续存在。 在黑暗中，动物必须对自己的运动进行内部评估，以更新它们的感觉 位置或方向。我们理解空间认知的下一步基本步骤是 描述引起这种生理活动模式的电路级相互作用，并了解 这些细胞最终是如何影响导航行为的我们最近的工作揭示了第一个神经回路 来解释当动物在黑暗中转身时，与头部相关的细胞如何更新它们的活动水平。本生物学 果蝇的脑回路是20年前哺乳动物脑回路的一种实现， 基于计算模型，但从未证明存在于任何动物中。在这里，我们重点介绍三个相关的 这些问题旨在更深入地了解大脑如何构建导航信号，以及 这些信号引导行为。我们的第一个目标是确定感觉信息到达的电路路径， 当动物在黑暗中转弯时，中央大脑会更新头部方向或航向系统。我们的第二 其目的是通过扰动航向信号的活动，确定航向信号在引导导航行为中的作用。 在动物中执行航向任务的航向相关细胞。我们的第三个目标是表征新的细胞类别 以及最终告知大脑如何解决二维导航任务的电路。总体 这项工作的目标是提供一个详细的，电路级的理解大脑如何计算空间导航- 相关变量。这些发现将为我们思考大脑如何让我们进行日常活动提供信息 导航任务，如下班开车回家或在停车场找到我们的车，以及如何接近 这些能力受损的精神和神经疾病，如阿尔茨海默病。

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 specific location in space), head-direction cells in the 1980’s (i.e., neurons that are active when animals face one specific 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 remarkable feature of these cells is that their patterns of firing persist even when animals navigate in complete darkness, wherein the animals must use an internal assessment of their own movements to update their sense of position or orientation. 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 cells ultimately influence navigational behavior. Our recent work has uncovered the first neural circuit to explain how heading-related cells update their activity levels when animals turn in the dark. This biological circuit in Drosophila is a realization of a circuit proposed to exist in the mammalian brain twenty years ago, based on computational modeling, but never proven to exist in any animal. Here we focus on three related questions that aim to provide a deeper understanding of how brains construct navigational signals and how these signals guide behavior. Our first aim is to identify a circuit path by which sensory information arrives to the central brain to update the head-direction or heading system when an animal turns in the dark. Our second aim is to determine the role of heading signals in guiding navigational behavior by perturbing the activity of heading-related cells in animals performing a heading task. Our third aim is to characterize new cell classes and circuitry to ultimately inform how brains might solve two-dimensional navigation tasks. The overarching goal of this work is to provide a detailed, circuit-level understanding of how brains compute spatial navigation- related variables. Such discoveries will inform our thinking on how our brains allow us to perform day-to-day navigation tasks, like driving home from work or finding our car in a parking lot, and how to approach psychiatric and neurological conditions in which these abilities are impaired, such as Alzheimer’s disease.