Cellular, columnar and modular organization of spatial representations in medial entorhinal cortex

•Grid cells in medial entorhinal cortex provide a metric representation of space.•Functional and anatomical evidence points to principal cell diversity, modularity and columnar organization in medial entorhinal cortex.•Intracellular recordings show that grid activity arises from recurring ramps of depolarization.

Spatial discharge patterns in medial entorhinal cortex consist of grid, head direction, border and spatial-band cells. These firing patterns differ from the single-peaked fields of hippocampal place cells, in that they have well-defined geometries and extend throughout the available space. Such discharge properties could contribute to a metric representation of space. Both functional and anatomical evidence point to principal cell diversity, modularity and columnar organization, but linking entorhinal anatomy and physiology remains challenging. Layer 2 microcircuits consist of pyramidal neurons and a stellate cell network, which lacks recurrent excitation and is coupled by disynaptic inhibition. Intracellular recordings showed that periodic, grid-like firing emerges from depolarization ramps, whereas theta-oscillations determine spike timing. Interference with various inputs to entorhinal cortex abolishes grid activity, often without concomitant loss of hippocampal place activity.