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

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Neural representations of direction and location are evident in the spatially selective firing or head direction (HD) and place cells, respectively. Place cells receive inputs from grid cells, and, putatively, boundary/border (B/B) cells. How these representations relate to one another and how they underlie spatial cognition is poorly understood. We will address this gap in our knowledge by exploiting the phenomenon of place cell repetition.

1) We will test whether the B/B cells, grid cells, and HD cells are sensitive to the orientation of local environments. We have demonstrated such a sensitivity for hippocampal place cells, where place fields repeat in environments that face the same direction, but not for those facing different directions (Grieves et al., 2015). We hypothesise that this sensitivity to direction arises from HD cell inputs to B/B cells.

2) To directly assess they hypothesis that HD cells drive B/B cell spatial firing, we will test whether removal of the HD cell system (via lesions of the lateral mammillary nuclei (LMN), essential for the generation of the HD signal) causes a loss of sensitivity to local environment orientation in B/B cells.

3) Thirdly, we will test the hypothesis that the HD cell system is necessary to distinguish local environments which face different directions. This will be done using a novel odour/location discrimination task that we have developed, which is particularly sensitive to direction.

4) In the final experiment, we will test whether it is the projections from the LMN to the anterior dorsal thalamus (AD) that are involved specifically in disambiguating local environments facing different directions. We predict that when the LMN -> AD connections are inhibited, place cells and B/B cells will be insensitive to the orientation of local environments.

Together, these experiments have the potential to link the HD cell system with representations of location, and with spatial discrimination learning.

Who will benefit from this work?

The proposed work is comprised of basis research on how the neural systems that represent direction interact with the neural systems that represent locations. Potential beneficiaries of this work beyond fellow researchers will likely include individuals with an interest in spatial cognition (e.g., those interested in navigation systems or their design), patients and caregivers of patients with topographical disorientation or Alzheimer's disease (where difficulties in spatial location recognition are common), designers of care homes and students interested in learning and memory.

How will they benefit?

Robust representations of location and direction are found in the spatially-tuned firing of place cells, grid cells, boundary/border cells and head direction cells, but how these different representations fit together to guide spatial cognition is not understood. The proposed studies will attempt to link between these representations, and thereby identify the basic brain circuit underlying the discrimination of local environments.

Understanding the normal representation of orientation may provide the standard from which abnormal brain function can be estimated. To be specific, in pathological conditions such as Alzheimer's disease, loss of neurons in the entorhinal cortex occurs early in condition. This same brain region contains the types of neurons - head direction cells and boundary/border cells - that will be manipulated in the current experiments. Thus, understanding how these neurons function in the intact brain, may allow development of, for example, early diagnostic tests based on an impaired direction sense.

Understanding how neural representations of direction contribute to the ability to discriminate environments with similar features may also have implications for the design of care homes. There is evidence that aged individuals have difficulties navigating within nursing homes (Passini et al., 2000). Our work may indicate that a sense of direction facilitates the discrimination of similar environments when they face different directions. If such a finding reflects a basic principle of spatial cognition, it could be used to improve the design of residential facilities with multiple, similar rooms. To that end, we will organise a set of workshops on neuroscience and design, which will bring together neuroscientists and architects to consider how neural representations of space might be leveraged to enhance design (see Pathway to Impact document).

The proposed work may benefit students interested in learning and memory by providing a template for understanding how other forms of cognition operate. In addition, characterizing the relationship between representations of direction and location could be applied to the design of mobile robots.