A critical appraisal of the what-where-when episodic-like memory test in rodents: Achievements, caveats and future directions.

ABSTRACT

During the last decade the what, where and when (WWWhen) episodic-like memory (ELM) task, which is based on the object recognition paradigm, has been utilized for the cognitive phenotyping of mouse mutants and transgenic mouse models of neuropsychiatric diseases. It was also widely used to identify the neuroanatomical, electrophysiological and pharmacological foundations of ELM formation, retention and retrieval. Findings from these studies have helped to increase our understanding of the neurobiology and neuropathology of episodic memory in the context of neurodegenerative and neuropsychiatric diseases. Pharmacological studies identified novel targets that might facilitate episodic memory formation in patients with memory problems. In this review, we attempt to delineate the cognitive operations and processes that might underlie rodent performance in the WWWhen/ELM task. We discuss major issues of the object recognition paradigm, including the problem of familiarity vs. recollection-based object recognition, the problem of novel object-induced neophobia, and propose novel methodological solutions to these issues. In conclusion, the WWWhen/ELM task has proven to be a useful tool in the fields of behavioral and translational clinical neuroscience and has the potential to be further refined to address major problems in animal memory research.