Grid cells contribution to distance coding and update of cognitive maps – GRIDSPACES

Navigation using an internal representation of the environment or a cognitive map requires allothetic information about the spatial arrangement of the landmarks and idiothetic (self-motion) information. Grid cells in the medial entorhinal cortex (MEC) exhibit a striking grid-like firing pattern that tesselate the environment and are supposed to be mainly driven by idiothetic cues in order to compute distances travelled in the environment. However, this point of view has been challenged by several studies showing that grid cells are highly sensitive to allothetic (visual) cues suggesting that these cues might be important in the establishment of grid cells firing patterns. Finally, the grid cells population might be functionally more heterogeneous than previously thought as they are present in two populations of projecting cells in layer 2 of the MEC that are characterized by different morpho-functional properties: stellate and pyramidal cells.

Our general goal is to clarify grid cells functions by analyzing how they encode distance travelled and how they react to local contextual changes in a familiar environment (to update the cognitive map). To do so we will take advantage of the recent development of virtual reality: an efficient tool to modify environments instantaneously and in a very controlled and reliable way. In our set up, a head-fixed mouse is running back and forth on a virtual linear track in one out of four conditions that differ 1) in the richness of wall patterns (poor or rich linear track) and 2) in the availability of virtual 3D-objects inside the track (with or without object). Grid cells will be recorded while the animal is running in its familiar track before being exposed to a sudden change in the availability of the 3D-objects. We have already started to validate this protocol on hippocampal place cells. Preliminary results indicate that depending on the availability of wall patterns and 3D objects, place cells showed distance (firing at the same distance from start in both directions) or position coding (firing at the same position relative to the external visual cues). Interestingly, the paucity of wall patterns and 3D objects favored distance coding while the presence of 3D-objects favored position coding. Finally, place cells were very sensitive to local contextual changes of the environment as they ‘remapped’ when the availability of 3D-objects was modified. Thus this protocol enables us to study grid cells activity in conditions where distance or position coding is favored and to determine how they react to contextual changes in the environment

We would like to answer four questions. First, are grid cells exhibiting distance and/or position coding? Second how are grid cells influenced by local contextual changes in the environment? Third, are pyramidal and stellate grid cells in layer 2 functionally heterogeneous? To differentiate stellate and pyramidal grid cells we will express Channerhodopsin-2 in one of these two populations of MEC layer 2 neurons in order to identify them by their excitatory response to light. Last, are grid cells necessary for distance/position coding and/or the update of cognitive maps in hippocampal place cells? To answer this question we will test the effects of an optical inactivation of the medial septum, a manipulation known to affect the spatial periodicity of grid cells, on place cells recorded in the virtual linear track.

We believe that answering our four questions will be essential to understand the function of grid cells in spatial cognition. As grid cells are present in layer 2 of the MEC, one of the first region to be affected in Alzheimer’s disease, we think that a clear functional characterization of this layer is a prerequisite to develop new therapeutics aimed at ameliorating memory deficits seen in this illness.