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

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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.