Protocol Episodic-like memory in mice: Simultaneous assessment of object, place and temporal order memory Ekrem Dere * , Joseph P. Huston, Maria A. De Souza Silva Institute of Physiological Psychology, Center for Biological and Medical Research, Heinrich-Heine-University of Du ¨ sseldorf, D-40225 Du ¨ sseldorf, Germany Accepted 15 August 2005 Available online 26 September 2005 Abstract 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. D 2005 Elsevier B.V. All rights reserved. Theme: Neural basis of behavior Topic: Learning and memory: systems and functions—animals Keywords: Novelty preference; Episodic-like memory; Hippocampus; Prefrontal cortex; Recency discrimination; Spatial memory 1. Type of research Simultaneous assessment of memory for ‘‘what’’, -‘‘where’’-and-‘‘when’’ in mice by combining different versions of the novelty preference paradigm. 1.1. Introduction In its narrowest sense, human episodic memory can be defined as the conscious recollection of the ‘‘what’’, -‘‘where’’-and-‘‘when’’ components of a unique personal experience, which can be verbally communicated to others. Since animals cannot verbalize a past experience, it was argued that they do not possess an episodic memory similar to humans [52]. However, nonverbal animals may instead possess an implicit form of episodic memory, i.e., the ability to remember the ‘‘what’’,-‘‘where’’-and-‘‘when’’ components of a unique episode, termed episodic-like memory, which can be operationalized at the behavioral level [16]. For example, food-caching scrub jays not only remember what kind of food they had stored and where they had stored it, but also how long ago they did this [11]. These birds obviously show an integrated memory for 1385-299X/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.brainresprot.2005.08.001 * Corresponding author. Fax: +49 211 81 12024. E-mail address: dere@uni-duesseldorf.de (E. Dere). Brain Research Protocols 16 (2005) 10 – 19 www.elsevier.com/locate/brainresprot