Episodic memory is relevant for auto-consciousness in humans. In nonhuman animals, episodic-like memory is defined when the "what-where-when" content of a unique event forms an integrated cognitive representation that is then deployed during memory retrieval. Here, we aimed at testing episodic-like memories of mice under experimental conditions that allow the analysis of whether and how mice process what-where-when information. Using an ecologically relevant paradigm for spontaneous learning and memory, we show that mice modulate their behavior based on the what, where, and when components of past unique episodes, specifically on previous encounters of conspecifics at a defined location and at a specific time of the day. We also show that learning during this paradigm activated Arc/Arg3.1 mRNA expression in the hippocampus and that stereotactic injection of anisomycin into this region impairs memory consolidation. Thus, hippocampus-dependent episodic-like memories of single experiences are spontaneously created in mice. These findings extend our knowledge of the cognitive capacities of the mouse and suggest that this species can be used as model for studying the mechanisms underlying human episodic memory and related neurological disorders.
