Elsevier

Progress in Neurobiology

Volume 130, July 2015, Pages 71-85
Progress in Neurobiology

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

https://doi.org/10.1016/j.pneurobio.2015.04.002Get rights and content

Highlights

  • The what, where and when (WWWhen)/episodic-like memory task has been utilized for the cognitive phenotyping of mutant and transgenic mice and in rodent models of neuropsychiatric diseases.

  • The use of the WWWhen test in gene-targeting, pharmacological, electrophysiological and lesion studies is reviewed.

  • Both methodological and theoretical issues are discussed and suggestions for further refinements of the WWW procedure are provided.

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.

Section snippets

General introduction and outline

Humans are capable of memorizing significant and personally important life events that were accompanied by increased emotional arousal (e.g. graduation days, car accidents). Moreover, memories of such emotional episodes can be recollected for a long period of time extending up to decades. On the other hand, we also encode, consolidate and retrieve less emotionally arousing events that happened within a period of a few days, and we are able to keep track of the sequence of events over the course

Neuroanatomy of ELM

Based on studies with patients suffering from hippocampal damage, it has been argued that episodic memory depends on intact hippocampal function (Tulving and Markowitsch, 1998). While there is strong evidence that some initially hippocampus-dependent memories can become independent from hippocampus with the passage of time during the course of consolidation (‘remote memory’; for review see Frankland and Bontempi, 2005), some theories, e.g., multiple trace theory, assume that especially episodic

A working hypothesis of the cognitive processes and dynamics involved in episodic-like memory formation

In order to have an idea of the various cognitive processes and dynamics that are involved in ELM formation in the WWWhen/ELM task developed by Dere et al., (2005b), and later on slightly modified by Kart-Teke et al. (2006) and Zlomuzica et al. (2007) we have now to think about the following central question: How is the animal possibly perceiving and processing the information presented during the sample and test trials? This information is crucial for the development of experimentally testable

Acknowledgements

This work was supported by Grant No. DFG-DE1149/6-1 to ED.

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