Is the cognitive map flat? A neurobiological study of spatial encoding in three dimensions.

One of the current most pressing questions in brain research concerns how the brain forms a mental map of the world: a necessary tool in order to be able to function normally while moving around in a complex world. Research has shown that this mental map, the so-called "cognitive map", depends on a network of structures deep inside the brain known as the hippocampal formation, of which the hippocampus itself is central. Interestingly, this hippocampal network is also critical for forming and storing memory for life events, leading neuroscientists to think that the brain uses its cognitive map as an organiser for all its memories. The importance and interrelatedness of these functions is evident in damage to this network, such as occurs in Alzheimer's disease, in which the first complaint of patients is often getting lost, and the culmination of which is profound amnesia.

Neuroscientists study the functioning of this network in a number of ways, but one of the most useful has been the technique of single neuron recording, where fine microwires are painlessly introduced into the brains of animals (usually rats, and more recently mice), in order to record the activity of brain cells (neurons) in these areas as the animal explores the world around. Since all mammal brains have the same basic plan, we also learn much about the human brain from these studies. Observation of the activity of hippocampal neurons has revealed that they are particularly active when the animal is at a particular place, hence their name "place cells". Each place cell has its own preferred place, and the question of how a place cell "knows" the animal is at that place has been of great interest. It recently took a great leap forward with the discovery of "grid cells", in a brain area immediately upstream of the place cells. Grid cells act like tiny odometers, in that they mark out distances in a very regular way, producing activity patterns that resemble the grid of a map (hence their name). Grid cells are important because they reveal the basic structure of the cognitive map.

Work on place and grid cells to date has focused on how they respond in a two-dimensional, flat world. However, the world is of course three-dimensional (3D), and it transpires that representing three dimensions is far more complicated than representing two, because animals can twist and turn within 3D space, making it very hard for the brain to keep track of orientation. We have begun to look at how place and grid cells respond when animals climb into the third, vertical dimension and have found that, amazingly, the distance-measuring properties of grid cells do not seem to extend into the vertical dimension. It is as if a grid cell does not "know" how high the rat is - and by extension, the cognitive map as a whole may not know this either. The implication is therefore that the cognitive map may be "flat".

This conclusion seems superficially surprising because we certainly have the subjective feeling that we possess an integrated 3D map of space. However, this feeling may be illusory, and the present project intends to find out if this is the case. We will record place and grid cells as rats and mice explore various environments, in order to find out whether the cells are sensitive to height or whether the map really is flat, and whether animals can navigate in ways that suggest they know about locations in 3D space. It may be, in fact, that the cognitive map really is 3D but that our previous experiments did not see this because of the restrictive kinds of apparatus that were used.

Answering the question of whether or not the cognitive map is 2- or 3D is of great importance in understanding our sense of space. This is true not only for scientists who seek to understand how the brain represents the world, but also for those who design 3d structures for humans to explore, including architects, and designers of space stations and of 3D virtual realities.

The aim of this project is to make recordings from spatially sensitive neurons - mainly grid cells - in rodent limbic cortex, to test the hypothesis that the neural representation of 3D space (the "cognitive map") is essentially planar. The hypothesis was motivated by our findings that place and grid cells show relduced sensitivity to vertical travel, as evidenced by the elongation of place fields and the absence of grid cell periodicity in the vertical dimension. In these experiments rats remained horizontally oriented while climbing, and possibly grid cell odometry does not operate in dimensions orthogonal to the direction of travel. Alternatively, it may be that regardless of how the rat is oriented, the cells do not encode distance travelled in the direction parallel to gravity. A final possibility is that the absent periodicity was an artefact of the surface structure of the apparatuses, and would re-appear if the animal could move freely in all 3 dimensions. The present proposal hopes to find out which of these is true, and in doing so, to determine how the 3D cognitive map is structured. The neural findings will then be related to behavioural findings from a 3D spatial maze, a variant of the Olton maze, in which animal forage using a win-shift rule. Of interest will be whether their foraging patterns are horizontally biased, as we have seen on other kinds of apparati, and also whether the animals are able to retain a working memory list of arms visited, even when these are distributed in 3D. This task will then be modified as a detour paradigm in which a usual route to a goal is blocked and the animal is forced to detour. Ability to plan detours is one of the hallmarks of cognitive mapping. If the map is planar, animals should use a layered strategy in foraging and may have trouble with the working memory and detour tasks. If they show behavioural evidence of an integrated 3D map, future work will determine which neural systems support this.

Who will benefit from this research?

The immediate beneficiaries of this research will be cognitive neuroscientists who seek to understand how cognitive representations are assembled by co-operative interactions between neurons. Similarly, behavioural and evolutionary ecologists will benefit from an enhanced understanding of how animals navigate and plan their behaviours in the 3D world in which they live. This is "blue sky" research whose impact is difficult to predict because it underpins the steady advancement of our understanding of how the brain works, which is one of science's greatest current goals. The impact in the longer term is thus potentially large, but hard to quantify.

Additional beneficiaries will be the neuroscience community more generally, who will benefit from the training of the new, upcoming generation of behavioural neuroscientists in in vivo recording techniques. Despite the value of these techniques for producing data that advance theoretical understanding or brain function, researchers with in vivo skills are scarce, especially in the UK. The PI has been heavily involved in trying to advance behavioural physiology, both by the establishment of the Institute of Behavioural Neuroscience at UCL, and also via a collaboration with Axona Ltd, the largest European supplier of behavioural recording systems, which has successfully developed portable, turnkey recording systems that do not require a high degree of technical sophistication to use. These systems are starting to attract behavioural scientists into the field, and will greatly enhance the behavioural sophistication of behavioural physiology experiments.

The work has translational implications in that the study of 3D spatial representation has the potential to advance such fields as aeronautics, and undersea and space exploration, in which disorientation is a notorious problem. It is also expected that designers of 3D virtual reality systems will benefit from the knowledge gained.

How will they benefit from this research?
The neuroscience community will benefit in two main ways: via publication of papers summarizing the findings, and by production of data which can be used for computational modelling.

The benefit from training new researchers will be by the continuation of these people into careers that use in vivo recording as a standard methodology, and start to combine it with other techniques such as pharmacology and genetics.

The translational impact will occur via scientific publications and other communications (conferences etc). Where applicable, follow-on funding will be sought to bring the findings to a wider audience.