On the Orientation of Entorhinal Grids

Abstract In the groundbreaking paper that eventually led to the 2014 Nobel prize in Physiology or Medicine, Hafting et al. (2005) reported that when rats forage for chocolate crumbs in a large open field, some neurons in their entorhinal cortex, called grid cells, exhibit crystalline-like responses to animal position, i.e. grids. Among several key findings documented in this article, the authors noted for the first time that the grids of different neurons can be tilted relative to each other, particularly if these neurons are far apart. In support of this claim, the researchers illustrated two neuronal subpopulations with a 7-10° difference in their grid orientations. Since these data are available online, we were able to reexamine these findings. Here we report several clarifications to the original observations of Hafting et al. First, we show that the relationship between the entorhinal grids is more complex than a single rotation: for the neuronal subpopulations analyzed by Hafting et al., one axis of the hexagonal grid is indeed tilted, but the other axes are not. Second, we show that local ensembles of entorhinal neurons are preferentially tuned to certain directions defined by the grid; this effect is unclear when single neurons are analyzed in isolation. Third, we argue that rat navigation traces are patterned instead of being random. For example, the orientation of the vector field representing average velocity appears to match the orientation of the neuronal grid. Overall, our observations indicate that additional insights into the function of entorhinal grids could be provided by ensemble-level analyses and thorough examination of the connection between the navigation behavior and neuronal patterns. Highlights While our examination of the online dataset from Hafting et al. generally confirms their original findings, several clarifications should be made. For the two neuronal subpopulations, where Hafting et al. reported a 7-10° relative tilt between the grids, only one of the grid axes is tilted, whereas the others are not. When spatial response fields are plotted for neuronal subpopulations instead of single neurons, it is clear that each subpopulation exhibits spatially periodic bands aligned with one of the grid axes. Navigation traces are not random and appear to match the orientation and periodicity of the neuronal grid.