Spatial and temporal representations are organized along a stable coding gradient in the medial entorhinal cortex

Abstract

The medial entorhinal cortex (MEC) has classically been viewed as a spatial coding region, but growing evidence indicates that it also contains temporal representations. However, how spatial and temporal codes are organized within the MEC remains unclear. Here we recorded MEC neurons with high-density silicon probes while mice performed a MEC-dependent timing task and a virtual reality spatial navigation task in a similar head-fixed setup. We found that spatial and temporal representations were partially overlapping but systematically biased across the MEC population. Grid cells and non-grid cells with strong spatial tuning were less likely to show reliable time-locked activity during the timing task. In contrast, neurons with weaker spatial tuning more flexibly shifted their coding scheme to temporal coding during timing task. Moreover, spatial tuning strength and its negative relationship with temporal tuning were preserved in a distinct open field environment, indicating that the coding preferences of individual neurons are constrained by a stable network-level organization. Together, these findings suggest MEC is organized along a coding gradient, ranging from dedicated stable spatial coding neurons to more flexible spatial or temporal coding neurons which represent information according to cognitive demands.