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

当我们导航时，我们通常依赖于大型可见地标来定位自己。例如，在乡村，我们可能会通过识别远处的山脉来定位自己，而在城市中，我们可能会根据一个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地标时，他们经常用啮齿动物进行基础实验研究。从这些研究中，我们知道哺乳动物大脑拥有代表当前位置的神经元，称为位置细胞。啮齿类动物的大脑也包含编码头部相对于外部世界的方向的神经元（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，这些类型的神经元的空间调谐放电可以由视觉标志控制，但位置细胞、头部方向细胞和网格细胞之间的关系还不完全清楚。一种可能性是头部方向信息或输入对于网格细胞的网格状放电是必要的，但这方面的证据并不明确。在拟议的实验中，我们将解决这个问题，通过比较删除相邻的大脑区域，其中一个是头方向细胞的来源（外侧乳头核），其中一个不是（内侧乳头核），对网格细胞放电的影响。我们预测头部方向神经元回路的损伤将破坏网格细胞的网格样放电，头部方向神经元如何控制视觉地标为基础的空间行为也不清楚。虽然对拥有定位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受损，但对具有头部方向细胞的结构的损伤的影响则不太清楚。然而，空间任务可以通过几种不同的方式来解决，其中只有一些需要与视觉地标的空间关联。为了明确测试头部方向细胞系统是否是基于地标的导航所必需的，我们将在新开发的空间地标测试中比较没有头部方向细胞系统的动物与对照动物的表现。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使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地标导航，没有头部方向系统的动物应该不会受损。一个相关的问题是，头部方向输入对于位置细胞激发位置的地标控制是否必要。这一点也将在目前的一系列研究中得到评估。拟议中的实验将告诉我们三件事。首先，它们将告诉我们头部方向细胞是否是网格细胞的网格状放电所必需的。第二，他们将告诉我们是否需要头部方向细胞系统来使用视觉地标进行导航。最后，建议的实验将告诉我们是否刺激控制的视觉地标的空间发射的地方字段取决于头部方向输入。因此，总的来说，本研究中的实验将阐明头部方向单元系统与网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基于地标的导航是必要的。这些是理解大脑如何处理空间地标以指导空间认知的重要步骤。

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.