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.

识别位置并在它们之间导航的能力对人类和其他活动动物来说都是必不可少的。神经生物学的一个核心问题是，哺乳动物的大脑是如何做到这一点的。解决这个问题最容易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相似，这种方法可以识别空间定向的基本机制。在目前的研究中，我们将使用神经元记录和大脑操作来观察位置和方向的神经表征是如何联系在一起的。在老鼠的大脑中，研究人员发现了“位置细胞”（place cell）和“头部方向细胞”（head direction cell），前者是对动物环境中的特定位置进行编码的细胞，后者是对生物体可能面对的特定方向进行调节的神经元。最近的发展包括在啮齿动物的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，它在距离环境边界给定的距离和方向上显示放电场。虽然我们对这些类型的空间细胞的个体特性了解很多，但我们不知道它们是如何相互作用来指导空间行为的。关于细胞如何相互作用的一个线索来自我们最近进行的一项研究。这是基于Spiers等人（2015）的发现，他们表明，在迷宫中，大鼠的位置细胞在四个平行的房间中显示出相似的区域。这表明位置细胞对局部地图进行编码，而这些地图在看起来相同的房间里是相似的。我们重复了这一实验，但发现如果房间面向不同的方向，位置细胞在迷宫房间中不会显示相似的区域（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，我们将利用这一现象来研究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，这产生了区分面对不同方向的相似环境的能力。为了验证这一点，我们将观察当动物在四个面向不同方向的相同迷宫间行走时，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定向敏感。在第二个系列实验中，我们将移除HD细胞系统（通过选择性地移除侧乳状核（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，并且在每个隔室中以相同的方式放电。在第三个系列实验中，我们将通过再次移除LMN来测试HD细胞系统是否有必要在行为上区分局部区室。在第四个系列的实验中，我们将针对LMN的假定HD投射（到丘脑前背侧，另一个包含头部方向细胞的大脑区域），以测试这些投射是否对重复隔室中的正交位置场至关重要。拟议的实验将解决关于方向和位置的表征如何在大脑中相互作用的基本问题。虽然我们对位置、高清、网格和B/B单元格的各个属性了解很多，但我们不知道这些表示是如何协同工作以指导无缝导航的。拟议中的实验将把这些系统联系起来，从而确定动物区分相似环境的一种机制，从而推动这一领域的发展。

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.