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Discovering the functional role of entorhinal grid cells

Supervisor: Dr Julija Krupic

Co-supervisor: Prof Ole Paulsen

The aim of this project is to determine the functional role of the medial entorhinal grid cells(1). These neurons are active in multiple fields arranged in a grid of equilateral triangles. Based on their periodic firing pattern, it has been proposed that they act as a universal metric of space. Our recent data has shown that grid cells become nonhomogeneous in polarized enclosures such as trapezoids(2), a result not predicted by the prevailing grid cell computational models. We have proposed an alternative hypothesis suggesting that the grid cell pattern arises from competing afferent hippocampal place cells. In this view, grid cells act as a matrix system that arranges information about individual locations in a topological order. This research will develop new behavioural assays to test these two hypotheses. The spatial cells in the parahippocampal-hippocampal formation will be recorded and manipulated to unravel the nature of their interactions. The medial entorhinal cortex is one of the first areas affected during the Alzheimer’s disease. Understanding the functional role it plays in navigation would be an important breakthrough in the much-needed early diagnosis of the disease.

Methods1

We will distort the geometric enclosure and study how it affects rat’s ability to find a goal location and how this correlates with recorded grid cell activity as well as the activity of other spatial cells. We will use wireless multi-tetrode drives and Neuropixels probes for multiple single unit recordings in mEC, CA1 and CA3.

Methods2

We will study how disruption of grid cell activity affects an animal’s ability to recognize the reward location based on a path-integration (i.e. its ability to measure distances). In this task, animals will be navigating in the virtual linear tracks. The activity of hippocampal cells will be recorded using two-photon imaging.

References

Hafting, T., Fyhn, M., Molden, S., Moser, M.-B. & Moser, E. I. Microstructure of a spatial map in the entorhinal cortex. Nature 436, 801–806 (2005)

Krupic, J., Bauza, M., Burton, S., Barry, C. & O’Keefe, J. Grid cell symmetry is shaped by environmental geometry. Nature 518, 232–235 (2015)

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