Landmark processing in the mammalian brain: do head direction cells drive grid cells and spatial behaviour?

哺乳动物大脑中的标志性处理：头部方向细胞驱动网格细胞和空间行为吗？

• 批准号: BB/L000040/1
• 负责人: Paul Dudchenko
• 金额: $ 22.52万
• 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: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL000040%2F1
• 关键词: Landmark; processing; mammalian; brain; do

When we navigate, we typically rely on large visible landmarks to orient ourselves. For example, in the country, we might orient ourselves by recognising a distant mountain range, while in a city we might orient based on a particularly salient building. How these landmarks are processed by the brain is the central question of the proposed experiments.When researchers attempt to understand how landmarks are processed by the brain, they often conduct basic experimental studies with rodents. From these studies, we know that the mammalian brain possesses neurons that represent current location, termed place cells. The rodent brain also contain neurones that encode head direction relative to the outside world (called head direction cells), and, more recently, neurons that possess grid-like firing fields within an environment (termed grid cells). Importantly, the spatially tuned firing of each of these types of neurones can be controlled by a visual landmark.How place-, head direction- and grid cells relate to one another is not fully understood. One possibility is that head direction information or inputs are necessary for the grid-like firing of grid cells, but the evidence for this is not clear cut. In the proposed experiments, we will address this issue by comparing the effect of removing adjacent brain regions, one of which is a source of head direction cells (the lateral mammillary nucleus), and one of which is not (the medial mammillary nucleus), on the firing of grid cells. We predict that lesions of the head direction cell circuit will disrupt the grid-like firing of grid cells.How head direction neurones control to visual landmark-based spatial behaviour is also unclear. Whereas damage to the brain region that possesses place cells, the hippocampus, produces profound impairments in spatial navigation relative to landmarks, the effects of damage to structures with head direction cells is much less clear. However, spatial tasks can be solved in several different ways, only some of which require a spatial association with a visual landmark. To explicitly test whether the head direction cell system is necessary for landmark based navigation, we will compare the performance of animals without a head direction cell system to control animals on a newly developed spatial landmark test. If head direction cells are necessary for using visual landmarks, the animals that lack these should show an impaired ability to use a landmark to find a hidden food reward. Conversely, if other neural systems are sufficient to enable landmark navigation, animals without a head direction system should be unimpaired. A related question is whether head direction inputs are necessary for landmark control over the location where place cells fire. This too will be assessed in the current set of studies.The proposed experiments will tell us three things. First, they will tell us whether head direction cells are necessary for the grid-like firing of grid cells. Second, they will tell us whether the head direction cell system is needed for using visual landmarks to navigate. Finally, the proposed experiments will tell us whether the stimulus control of visual landmarks over the spatial firing of place fields depends on a head direction input. Thus, overall, the experiments in this grant will clarify the relationship between the head direction cell system and the grid- and place cell systems, and will test whether the head direction cell system is necessary for landmark-based navigation. These are important steps in understanding how the brain processes spatial landmarks to guide spatial cognition.

当我们导航时，我们通常依靠巨大的可见地标来定位自己。例如，在乡下，我们可能会通过认出远处的山脉来确定自己的方位，而在城市里，我们可能会根据一座特别突出的建筑来定位。大脑如何处理这些地标是拟议实验的中心问题。当研究人员试图了解大脑如何处理这些地标时，他们通常会对啮齿动物进行基础实验研究。从这些研究中，我们知道哺乳动物的大脑拥有代表当前位置的神经元，称为位置细胞。啮齿动物的大脑还包含编码相对于外部世界的头部方向的神经元(称为头部方向细胞)，以及最近在环境中拥有网格状发射场的神经元(称为网格细胞)。重要的是，每种类型神经元的空间调谐放电都可以由一个视觉地标控制。位置、头部方向和网格细胞如何相互联系尚不完全清楚。一种可能性是，头部方向信息或输入对于网格细胞的栅格样激发是必要的，但这方面的证据尚不清楚。在拟议的实验中，我们将通过比较移除邻近大脑区域对网格细胞放电的影响来解决这个问题，其中一个区域是头部方向细胞的来源(乳头状核外侧核)，而另一个不是(乳头体内侧核)。我们预测，头部方向神经元回路的损伤将扰乱网格细胞的网格状放电。头部方向神经元如何控制基于视觉地标的空间行为也不清楚。虽然拥有位置细胞的大脑区域--海马体--的损伤会导致相对于地标的空间导航严重障碍，但对拥有头部方向细胞的结构的损伤的影响则不那么明显。然而，空间任务可以用几种不同的方法来解决，其中只有一些方法需要与视觉地标进行空间关联。为了明确测试基于地标的导航是否需要头部方向细胞系统，我们将在一项新开发的空间地标测试中比较没有头部方向细胞系统控制动物的表现。如果头部方向细胞是使用视觉地标所必需的，那么缺乏这些细胞的动物应该表现出利用地标寻找隐藏的食物奖励的能力受损。相反，如果其他神经系统足以实现里程碑式的导航，没有头部方向系统的动物应该不会受到损害。一个相关的问题是，头部方向输入是否是控制Place单元发射位置的里程碑所必需的。这一点也将在目前的一系列研究中进行评估。拟议的实验将告诉我们三件事。首先，他们将告诉我们，头部方向细胞是否是网格状细胞激活所必需的。其次，他们将告诉我们，使用视觉地标导航是否需要头部方向细胞系统。最后，所提出的实验将告诉我们，视觉地标对位置场空间激发的刺激控制是否依赖于头部方向输入。因此，总的来说，这项授权中的实验将澄清头部方向单元系统与栅格和位置单元系统之间的关系，并将测试头部方向单元系统是否对于基于地标的导航是必要的。这些都是理解大脑如何处理空间地标来指导空间认知的重要步骤。

项目成果

Place field repetition and spatial learning in a multicompartment environment.

• DOI: 10.1002/hipo.22496
• 发表时间: 2016-01
• 期刊: Hippocampus
• 影响因子: 3.5
• 作者: Grieves RM;Jenkins BW;Harland BC;Wood ER;Dudchenko PA
• 通讯作者: Dudchenko PA

Place cells on a maze encode routes rather than destinations.

• DOI: 10.7554/elife.15986
• 发表时间: 2016-06-10
• 期刊: eLife
• 影响因子: 7.7
• 作者: Grieves RM;Wood ER;Dudchenko PA
• 通讯作者: Dudchenko PA

The head direction cell system and behavior: The effects of lesions to the lateral mammillary bodies on spatial memory in a novel landmark task and in the water maze.

• DOI: 10.1037/bne0000106
• 发表时间: 2015-12
• 期刊: Behavioral neuroscience
• 影响因子: 1.9
• 作者: Harland B;Wood ER;Dudchenko PA
• 通讯作者: Dudchenko PA