Spatial orientation and the brain: identifying the link between neural representations of direction and location

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The ability to recognise locations and navigate between them is essential for both humans and other mobile animals. A central question in neurobiology is how the mammalian brain achieves this. One of the most tractable ways in which this can be addressed is by recording neurones in specific areas of the rodent brain. As the essential structure of the rodent brain is similar to that of other mammals, including humans, this approach allows identification of the basic mechanisms for spatial orientation. In the current research, we will use neuronal recordings and brain manipulations to see how neural representations of location and direction are linked.In the rat brain, researcher have discovered place cells, which encode specific locations in an animal's environment, and head direction (HD) cells, which are neurons that are tuned to the specific direction and organism might face. More recent developments include the discovery of grid cells in the rodent medial entorhinal cortex. These cells show repeated, grid-like firing patterns as the animal explores and enclosed environment. An additional type of spatially-tuned neuron is the boundary/border (B/B) cell, which exhibits a firing field a given distance and direction from an environmental boundary. Although much is known about the individual properties of these types of spatial cells, what is not known is how they interact to guide spatial behaviour.One clue about how cells interact arises from a recent study that we conducted. It was based on findings by Spiers et al. (2015), who had shown that place cells in the rat show similar fields across four, parallel rooms in a maze. This suggests that place cells encode local maps, and that these maps are similar in rooms that look the same. We replicated this, but found that place cells do not show similar fields across maze rooms if the rooms face different directions (Grieves et al., 2015). Together, these results suggest that place cells are driven by room boundaries and by inputs which encode direction. In the proposed experiments, we will exploit this phenomenon to study how HD cells interact with place cells. Our hypothesis is that HD cells underlie the spatial firing of B/B cells, and that this gives rise to the ability to discriminate similar environments which face different directions. To test this, we will see whether head direction cells show an unchanged preferred firing direction when the animal travels between four identical maze compartments which face different directions. We will also test whether B/B cells are sensitive to the global orientation of local compartments. In a second series of experiments, we will remove the HD cell system (by selectively removing the lateral mammillary nuclei (LMN), a brain region critical for generating the head direction signal). In rats without the LMN, we predict that B/B cells will no longer discriminate between the direction of local compartments, and will fire in the same way in each compartment.In a third series of experiments, we will test whether the HD cell system is necessary to tell local compartments apart behaviourally by again removing the LMN. In the fourth series of experiments, we will target the putative HD projections of the LMN (to the anterior dorsal thalamus, another brain region containing head direction cells), to test whether it is these projections specifically that are essential for orthogonal place fields in repeated compartments.The proposed experiments will address basic questions about how representations of direction and location in the brain interact. Though much is known about the individual properties of place, HD, grid, and B/B cells, what is not known is how these representations work together to guide seamless navigation. The proposed experiments will advance the field by linking these systems, and thereby identifying one mechanism by which animals can distinguish similar environments.