Panoz-Brown, Danielle, Iyer, Vishakh, Carey, Lawrence M., Sluka, Christina M., Rajic, Gabriela, Kestenman, Jesse, Gentry, Meredith, Brotheridge, Sydney, Somekh, Isaac, Corbin, Hannah E., Tucker, Kjersten G., Almeida, Bianca, Hex, Severine B., Garcia, Krysten D., Hohmann, Andrea G., and Crystal, Jonathon D.
Summary 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. [ABSTRACT FROM AUTHOR]