Episodic-like memory in mice: simultaneous assessment of object, place and temporal order memory.

Episodic memory refers to the conscious recollection of a unique past experience in terms of "what" happened and "where" and "when" it happened. Since deficits in episodic memory are found in a number of neuropsychiatric diseases, such as Alzheimer's disease, for which several pharmacological, lesion and genetic animal models are available, there is a need for animal models of episodic-like memory, which can be used to devise appropriate treatments. However, even when the problem of conscious recollection in animals is factored out, episodic memory has been difficult to demonstrate in nonhuman mammals because it has not yet been possible to demonstrate an integrated memory for "what",-"where"-and-"when". We designed a three-trial "what",-"where"-and-"when" object exploration task in which different versions of the novelty preference paradigm were combined to subsume (a) object recognition memory, (b) the memory for locations in which objects were explored and (c) the temporal order memory for objects presented at distinct time points. Our results suggest that mice are able to (a) recognize previously explored objects, (b) remember the location in which particular objects were previously encountered and (c) discriminate the relative recency in which different objects were presented. We suggest that our protocol providing the simultaneous assessment of object memory for "what",-"where"-and-"when" in mice might be useful in the search for the neural substrates of episodic memory, the screening for promnestic drugs and the behavioral phenotyping of genetic models of neuropsychiatric diseases affecting episodic memory.