Distinct contributions of the hippocampus and medial prefrontal cortex to the “what–where–when” components of episodic-like memory in mice

There is a current controversy regarding whether non-human animals have a capacity for episodic memory, defined by the ability to remember what happened and where and when it occurred. It is also unclear which brain structures support the “what,” “where,” and “when” aspects of episodic memory. Here we addressed these issues by testing episodic memory in mice, using an object recognition task that has previously been employed to assess the “what,” “where,” and “when” components of recognition memory. Whereas intact mice remembered which objects they had explored, as well as when and where they were experienced, mice with damage to the hippocampus were impaired on all three components of the task. In contrast, animals with medial prefrontal cortical lesions were selectively impaired on the “where” component of the task, but had intact memory for “what” and “when.” These results are consistent with the hypothesis that the hippocampus integrates the “what,” “where,” and “when” features of unique experiences, whereas the prefrontal cortex makes a more selective contribution to retrieving source information about where events occurred.