Spatial orientation and the brain: identifying the link between neural representations of direction and location

空间定向和大脑：识别方向和位置的神经表征之间的联系

• 批准号: BB/P001726/1
• 负责人: Paul Dudchenko
• 金额: $ 21.88万
• 依托单位: University of Stirling
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP001726%2F1
• 关键词: Spatial; orientation; brain; identifying; link

The ability to recognise locations and navigate between them is essential for both humans and other mobile animals. A central question in neurobiology is how the mammalian brain achieves this. One of the most tractable ways in which this can be addressed is by recording neurones in specific areas of the rodent brain. As the essential structure of the rodent brain is similar to that of other mammals, including humans, this approach allows identification of the basic mechanisms for spatial orientation. In the current research, we will use neuronal recordings and brain manipulations to see how neural representations of location and direction are linked.In the rat brain, researcher have discovered place cells, which encode specific locations in an animal's environment, and head direction (HD) cells, which are neurons that are tuned to the specific direction and organism might face. More recent developments include the discovery of grid cells in the rodent medial entorhinal cortex. These cells show repeated, grid-like firing patterns as the animal explores and enclosed environment. An additional type of spatially-tuned neuron is the boundary/border (B/B) cell, which exhibits a firing field a given distance and direction from an environmental boundary. Although much is known about the individual properties of these types of spatial cells, what is not known is how they interact to guide spatial behaviour.One clue about how cells interact arises from a recent study that we conducted. It was based on findings by Spiers et al. (2015), who had shown that place cells in the rat show similar fields across four, parallel rooms in a maze. This suggests that place cells encode local maps, and that these maps are similar in rooms that look the same. We replicated this, but found that place cells do not show similar fields across maze rooms if the rooms face different directions (Grieves et al., 2015). Together, these results suggest that place cells are driven by room boundaries and by inputs which encode direction. In the proposed experiments, we will exploit this phenomenon to study how HD cells interact with place cells. Our hypothesis is that HD cells underlie the spatial firing of B/B cells, and that this gives rise to the ability to discriminate similar environments which face different directions. To test this, we will see whether head direction cells show an unchanged preferred firing direction when the animal travels between four identical maze compartments which face different directions. We will also test whether B/B cells are sensitive to the global orientation of local compartments. In a second series of experiments, we will remove the HD cell system (by selectively removing the lateral mammillary nuclei (LMN), a brain region critical for generating the head direction signal). In rats without the LMN, we predict that B/B cells will no longer discriminate between the direction of local compartments, and will fire in the same way in each compartment.In a third series of experiments, we will test whether the HD cell system is necessary to tell local compartments apart behaviourally by again removing the LMN. In the fourth series of experiments, we will target the putative HD projections of the LMN (to the anterior dorsal thalamus, another brain region containing head direction cells), to test whether it is these projections specifically that are essential for orthogonal place fields in repeated compartments.The proposed experiments will address basic questions about how representations of direction and location in the brain interact. Though much is known about the individual properties of place, HD, grid, and B/B cells, what is not known is how these representations work together to guide seamless navigation. The proposed experiments will advance the field by linking these systems, and thereby identifying one mechanism by which animals can distinguish similar environments.

识别位置并在位置之间导航的能力对于人类和其他移动动物来说至关重要。神经生物学的一个中心问题是哺乳动物的大脑如何实现这一目标。解决这个问题的最容易处理的方法之一是记录啮齿动物大脑特定区域的神经元。由于啮齿动物大脑的基本结构与包括人类在内的其他哺乳动物的大脑结构相似，因此这种方法可以识别空间定向的基本机制。在当前的研究中，我们将使用神经元记录和大脑操作来了解位置和方向的神经表征是如何联系起来的。在大鼠大脑中，研究人员发现了位置细胞（编码动物环境中的特定位置）和头部方向（HD）细胞，头部方向（HD）细胞是针对特定方向和生物体可能面临的神经元。最近的进展包括在啮齿动物内侧内嗅皮层中发现网格细胞。当动物探索和封闭的环境时，这些细胞显示出重复的、网格状的放电模式。另一种类型的空间调谐神经元是边界/边界（B/B）细胞，它在距环境边界给定距离和方向的情况下表现出发射场。尽管人们对这些类型的空间细胞的个体特性了解很多，但尚不清楚它们如何相互作用以指导空间行为。关于细胞如何相互作用的一条线索来自我们最近进行的一项研究。它是基于 Spiers 等人的发现。 (2015)，他证明大鼠体内的位置细胞在迷宫中的四个平行房间中显示出相似的区域。这表明位置细胞编码局部地图，并且这些地图在看起来相同的房间中是相似的。我们复制了这一点，但发现如果房间面向不同的方向，位置细胞不会在迷宫房间中显示相似的场（Grieves et al., 2015）。总之，这些结果表明位置细胞是由房间边界和编码方向的输入驱动的。在拟议的实验中，我们将利用这种现象来研究 HD 细胞如何与位置细胞相互作用。我们的假设是 HD 细胞是 B/B 细胞空间放电的基础，这产生了区分面向不同方向的相似环境的能力。为了测试这一点，我们将观察当动物在面向不同方向的四个相同的迷宫隔间之间移动时，头部方向细胞是否显示出不变的首选发射方向。我们还将测试 B/B 细胞是否对局部区室的全局方向敏感。在第二个系列的实验中，我们将移除HD细胞系统（通过选择性地移除侧乳头核（LMN），这是产生头部方向信号的关键大脑区域）。在没有 LMN 的大鼠中，我们预测 B/B 细胞将不再区分局部隔室的方向，并且将以相同的方式在每个隔室中放电。在第三个系列的实验中，我们将测试 HD 细胞系统是否有必要通过再次去除 LMN 来在行为上区分局部隔室。在第四个系列的实验中，我们将瞄准 LMN 的假定 HD 投影（到前背侧丘脑，另一个包含头部方向细胞的大脑区域），以测试这些投影是否对于重复区室中的正交位置场至关重要。所提出的实验将解决有关大脑中方向和位置的表示如何相互作用的基本问题。尽管人们对地点、HD、网格和 B/B 单元的各个属性了解很多，但尚不清楚这些表示如何协同工作以指导无缝导航。拟议的实验将通过连接这些系统来推进该领域的发展，从而确定动物可以区分相似环境的一种机制。

项目成果

Navigating space in the mammalian brain.

哺乳动物大脑中的空间导航。

• DOI: 10.1126/science.abi9663
• 发表时间: 2021
• 期刊: Science (New York, N.Y.)
• 作者: Wood ER

Lesions of the Head Direction Cell System Increase Hippocampal Place Field Repetition.

• DOI: 10.1016/j.cub.2017.07.071
• 发表时间: 2017-09-11
• 期刊: Current biology : CB
• 作者: Harland B;Grieves RM;Bett D;Stentiford R;Wood ER;Dudchenko PA
• 通讯作者: Dudchenko PA

Lesions of the head direction cell system impair direction discrimination.

头部方向细胞系统的损伤会损害方向辨别能力。

• DOI: 10.1037/bne0000341
• 发表时间: 2019
• 期刊: Behavioral neuroscience
• 影响因子: 1.9
• 作者: Smith AE

A boundary vector cell model of place field repetition

• DOI: 10.1080/13875868.2018.1437621
• 发表时间: 2018-01-01
• 期刊: SPATIAL COGNITION AND COMPUTATION
• 影响因子: 1.9
• 作者: Grieves, Roddy M.;Duvelle, Eleonore;Dudchenko, Paul A.
• 通讯作者: Dudchenko, Paul A.