Prior experience dynamically determines differential cue weighting in the medial entorhinal cortex

Spatial navigation depends on integrating multiple cue sets whose influence is determined primarily by their inferred reliability. Here we investigated how cue weighting in the medial entorhinal cortex is updated based on previous experience at different time scales (minutes vs. days). In mice recorded in light and darkness while manipulating coherence between distal room cues and local arena cues, grid cells displayed stable firing fields in darkness only when prior light experience maintained coherent cue relationships. Grid activity remained anchored to local cues, and stability continuously increased by repeated exposure. In contrast, mice that experienced cue mismatch in light showed markedly reduced grid stability in darkness. Strikingly, re-establishing cue coherence produced only partial recovery, whereas a single exposure to cue mismatch abolished reliance on local cues. The reference frame shift at different time scales reflects a dynamic balance between flexibility and stability determined by a conservative cue weighting strategy.