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Curr Biol. 2018 May 21;28(10):1628-1634.e7. doi: 10.1016/j.cub.2018.04.006. Epub 2018 May 10.

Replay of Episodic Memories in the Rat.

Author information

1
Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
2
Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN 47405, USA; Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405, USA.
3
Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN 47405, USA. Electronic address: jcrystal@indiana.edu.

Abstract

Vivid episodic memories in people have been characterized as the replay of multiple unique events in sequential order [1-3]. The hippocampus plays a critical role in episodic memories in both people and rodents [2, 4-6]. Although rats remember multiple unique episodes [7, 8], it is currently unknown if animals "replay" episodic memories. Therefore, we developed an animal model of episodic memory replay. Here, we show that rats can remember a trial-unique stream of multiple episodes and the order in which these events occurred by engaging hippocampal-dependent episodic memory replay. We document that rats rely on episodic memory replay to remember the order of events rather than relying on non-episodic memories. Replay of episodic memories survives a long retention-interval challenge and interference from the memory of other events, which documents that replay is part of long-term episodic memory. The chemogenetic activating drug clozapine N-oxide (CNO), but not vehicle, reversibly impairs episodic memory replay in rats previously injected bilaterally in the hippocampus with a recombinant viral vector containing an inhibitory designer receptor exclusively activated by a designer drug (DREADD; AAV8-hSyn-hM4Di-mCherry). By contrast, two non-episodic memory assessments are unaffected by CNO, showing selectivity of this hippocampal-dependent impairment. Our approach provides an animal model of episodic memory replay, a process by which the rat searches its representations in episodic memory in sequential order to find information. Our findings using rats suggest that the ability to replay a stream of episodic memories is quite old in the evolutionary timescale.

KEYWORDS:

DREADD; episodic memory; episodic replay; familiarity; hippocampus; rat; replay

PMID:
29754898
PMCID:
PMC5964044
[Available on 2019-05-21]
DOI:
10.1016/j.cub.2018.04.006

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