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

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.

Salient visual landmarks exert stimulus control over spatial behaviour, and over the spatial firing of place-, head direction- and grid cells. How these representations relate to one another, and how they contribute to landmark-based spatial behaviour, is not fully understood. The proposed experiments will address this gap in our knowledge, using a targeted removal of the head direction cell circuit as a probe.

In a first experiment, we will lesion the lateral mammillary nucleus (LMN, an essential component of the head direction cell system) or the adjacent medial mammillary nucleus (MMN), and record from the medial entorhinal cortex (MEC). We predict that LMN lesions will abolish the direction tuning of head direction cells in the MEC, as well as the grid-like firing of grid cells there. In contrast, MMN lesions should spare HD cell directional activity, although disruption of grid cell firing is possible because of an altered theta input from this region.

In a second experiment, we will test if the head direction cell circuit is necessary for landmark-based navigation. We will use a newly devised landmark/reward task, and compare control animals to those with lesions of either the LMN or the hippocampus. We predict that the former will not impair navigation, while the latter will exhibit a clear impairment. Such a pattern of results in a single study would establish a clear contrast between the HD cell and place cell contributions to landmark-based navigation.

In a final experiment, we will test whether the head direction input is necessary for landmark control over hippocampus place cell fields. If lesions impair landmark control over place fields, it would suggest that the head direction input is essential for landmark/location associations. If an impairment is not observed, it would suggest that these associations depend on a non-head direction input from the postsubiculum.

The proposed work is comprised of basic systems neuroscience research on how the brain represents spatial information, and how spatial landmarks control these representations and spatial behaviour. Potential beneficiaries of this work beyond fellow researchers may include individuals with an interest in spatial cognition (e.g., those interested in navigation systems or their design, mountaineers), patients and caregivers of patients with topographical disorientation or Alzheimer's disease (where difficulties in spatial location recognition are common), and students interested in learning and memory.

The proposed studies will provide a benefit to these groups by providing a more concrete idea of how spatial information is processed by the brain. So, for example, if we learn that the neural representation of direction is necessary for the firing of grid cells, it might suggest a neural network that could be applied to the design mobile robots. Knowledge that disruption of the head direction system does (or does not) disrupt landmark-based navigation may be helpful in understanding the precise deficits in patients who are unable to use landmarks to guide their spatial responses (e.g., if disruption of the head direction system does not yield landmark/reward deficits, it may imply that the underlying deficit in some forms of topographical disorientation are not directional per se, but rather are related to a landmark processing deficit). Students interested in learning and memory might benefit as understanding how the head direction/grid/place cell network functions may provide a template for understanding how other forms of cognition operate, or how this same network also contributes to episodic memory representations.