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GRIDCODE Report Summary

Project ID: 338865
Funded under: FP7-IDEAS-ERC
Country: Norway

Mid-Term Report Summary - GRIDCODE (Cortical maps for space)

With the discovery of grid cells as the brain´s metric for space in 2005, spatial navigation became one of the first non-sensory ‘cognitive’ functions of the brain to be accessible for mechanistic analysis. Because the hexagonally patterned firing of these cells is generated within the brain, in elaborate neural circuits far away from specific sensory inputs, grid cells provide us with unprecedented access to algorithms of neural coding in the higher cortices. GRIDCODE takes advantage of this emerging opportunity. The overall objective of GRIDCODE is to decipher how function is coded, divided and integrated among components of the grid-cell circuit. Using a combination of transgenic interventions, multisite multichannel tetrode recording and optical imaging, we aim to determine the number and distribution of grid modules, their organization and mechanisms, and their relationship to place cells in the hippocampus.

The work is organized into 6 workpackages (WP). In WP1, we determine the number of grid modules and their distribution within the medial entorhinal cortex (MEC). Results so far suggest that grid cells are expressed widely across both the mediolateral and dorsoventral extents of the circuit. We are developing technology for wireless recording in large enviornments in order to determine the presence and distribution of grid-cell modules with long spatial wavelengths in the ventral regions of the MEC. In WP2, we determine the scale relationship between grid modules and their sensitivity to properties of the environment. We have shown that grid patterns undergo transformations that can be described simply and precisely by shear forces along the cardinal axes of the environment. Ongoing work aims to compare scale factors of different species (rats and mice) with different absolute values for grid spacing. In WP3, we determine if the modular organization of grid cells is expressed from the beginning of MEC development or if modules develop gradually or are added in a particular order. We have developed methods to label selectively cells that are born on a specific day of embryonic development and we have shown that dorsal MEC stellate cells are born first, and that more ventral cells are added on in a strictly dorso-ventral sequence. We are currently establishing whether birth date can be related to module formation. In WP4, we determine how grid cells in different layers of MEC depend on each other. We have shown that inactivation of MEC layer II cells does not influence grid formation in deeper layers, or even in layer II itself, in any significant way, suggesting that there is considerable redundancy in the local inputs needed to form a grid pattern. We have also shown that Arch-expressing layer II cells include both stellate cells and border cells, with a slight preference for stellate cells. The findings have also revealed the presence of speed cells, cells whose firing rates increase linearly with running speed. These cells are likely to update grid cells with positional information at millisecond frequencies. In WP5, we use a rabies virus-based monotranssynaptic tracing approach to determine the functional identity of MEC cells with direct connections to an identified hippocampal cell. Information about inputs to individual cells will help us establish the mechanism for transformation of spatial activity in MEC to place-cell activity in the hippocampus. We are making significant progress on developing the functional tracing technology and are now seeing labelling in specific entorhinal input neurons as a result of rabies infection of very low numbers of cells in the hippocampus in anaesthetized animals. Finally in WP6, we record simultaneously from large numbers of neurons in the hippocampus and the MEC in order to determine whether patterns of input from modules of grid cells contribute to the formation of place fields in principal cells of the hippocampus. Technology for parallel recording from the two structures is still under development but we have shown by selective chemogenetic silencing that activity in MEC cells is necessary for induction of remapping in place cells of the hippocampus. All in all, every WP is on track, with some modifications in experimental approaches, but we expect all major goals to be reached by the end of the project period.

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