Highlights d Inferential decisions engage the hippocampus in humans and mice d During inference, a hippocampal prospective code draws on associative memories d This hippocampal prospective code preserves the learned temporal statistics d During rest, hippocampal ripples nest cognitive shortcuts for inferred relations

The hippocampus provides the brain’s memory system with a subset of neurons holding a map-like representation of each environment experienced. We found in mice that optogenetic-silencing those neurons active in an environment unmasked a subset of quiet neurons, enabling the emergence of an alternative map. This intervention applied in a cocaine-paired environment neutralized an otherwise long-lasting drug-place preference, showing that recoding a spatial memory engram can alleviate associated maladaptive behavior.