Grid and Nongrid Cells in Medial Entorhinal Cortex Represent Spatial Location and Environmental Features with Complementary Coding Schemes

Abstract

Summary The medial entorhinal cortex (mEC) has been identified as a hub for spatial information processing by the discovery of grid, border, and head-direction cells. Here we find that in addition to these well characterized classes, nearly all of the remaining two thirds of mEC cells can be categorized as spatially selective. We refer to these cells as non-grid spatial cells and confirmed that their spatial firing patterns were unrelated to running speed and highly reproducible within the same environment. However, in response to manipulations of environmental features, such as box shape or box color, non-grid spatial cells completely reorganized their spatial firing patterns. At the same time, grid cells retained their spatial alignment and predominantly responded with redistributed firing rates across their grid fields. Thus, mEC contains a joint representation of both spatial and environmental feature content, with specialized cell types showing different types of integrated coding of multimodal information.

Viewpoints: how the hippocampus contributes to memory, navigation and cognition

“…Diehl et al . 109 reveal that the nongrid population, on the other hand, may be quite interesting—these cells, like CA1 place cells, show global remapping (i.e., a change in the corresponding spatial context representation) if sensory cues do not match previously known environments. This work nicely complements findings from Keene et al .…”

Grid scale drives the scale and long-term stability of place maps

“…1g). As MEC contains a large number of cells that encode the spatial location of the animal but do not show grid or border firing patterns 32, 33 , we then considered cells that significantly encoded P but were not classified as grid or border cells. We found no significant differences in multiple coding features of this population of P-encoding cells, consistent with our analyses of spatially modulated cells identified using shuffling (Fig.…”

Heterogeneity in hippocampal place coding

“…The middle and bottom panels depict the impact on grid and place cell activity, respectively. From left to right: Control recordings in a white rectangular arena; Large changes in environmental context resulted in realignment of the grid pattern and global remapping of place cells [36]; Smaller changes to environmental context altered to varying degrees the firing rate of individual grid nodes and induced rate remapping in place cells [27 • ]; Lesions of MEC that eliminate grid activity have largely resulted in increased place field size (similar effects were seen following muscimol inactivation of MEC, not shown) [38,40,76]; Optogenetic inhibition of MEC greatly reduced grid cell firing and drove remapping in place cells without impacting field size; MEC-specific knockout of HCN1 channels increased the scale of both grid and place cell representations (particularly amongst place fields located far from environmental boundaries) and decreased place cell stability [50 •• ]; Inactivation of medial septum (MS) largely eliminated the periodicity of grid cell firing patterns, with the impact on place cells including minimal effects on stability and large disruptions in the spatial coding of all place cells save those with fields near boundaries [44,45,49,76]. …”

“…The entorhinal cortex is subdivided into two primary functional regions: the lateral portion (LEC), which encodes non-spatial, contextual features such odor or objects and the medial portion (MEC), which encodes features associated with the location of an animal with respect to its environment and serves as a prime candidate to drive the spatial component of the hippocampal place code [23–26,27 • ]. Within MEC reside a number of functionally distinct, spatially modulated cell types that include grid cells that fire in periodic spatial locations, border cells that increase their firing rate near environmental boundaries, head direction cells that fire when an animal faces a particular direction and spatial cells with stable non-geometric spatial firing patterns [24–26,27 • ]. Initially, research focused on the hypothesis that input from grid cells with different phases and spatial scales could sum via a Fourier synthesis mechanism to yield a single downstream place field [20].…”