Replay of Episodic Memories in the Rat

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.

Transcending time in the brain: How event memories are constructed from experience

“…What has emerged from this body of work is a remarkable synergy between findings in humans and animals, thereby underscoring the evolutionarily conserved roles of these structures in episodic memory organization (Eichenbaum, ; Panoz‐Brown et al, , ; Preston & Eichenbaum, ). This research has also drawn intriguing parallels between the brain mechanisms that link events together either during learning or after longer delays (Schlichting & Frankland, ), raising the possibility that similar or complementary mechanisms are involved in the formation and integration of episodic memories at different timescales (Mau et al, ; Nielson, Smith, Sreekumar, Dennis, & Sederberg, ; Wirt & Hyman, ).…”

“…A wealth of studies in rodents shows that, during spatial navigation tasks, hippocampal place cells rapidly replay recent experiences in the order in which they occurred (Carr, Jadhav, & Frank, 2011;Foster & Wilson, 2006;Panoz-Brown et al, 2018). Such rapid neural replay has been hypothesized to be important for preserving memory for the sequential order of recent information, although more evidence supporting this hypothesis is needed (Ólafsdóttir, Bush, & Barry, 2018).…”

Number and time in acquisition, extinction and recovery

“…We take our results and those of others (Bratch et al, 2016;Crystal & Smith, 2014;Panoz-Brown et al, 2016;Panoz-Brown et al, 2018;Wilson, Mattell, & Crystal, 2015;Zhou, Hohmann, & Crystal, 2012) to suggest that the memory contents that drive classically conditioned behavior come from a hierarchically structured record of the episodes in the conditioning experience. We take our results and those of others (Bratch et al, 2016;Crystal & Smith, 2014;Panoz-Brown et al, 2016;Panoz-Brown et al, 2018;Wilson, Mattell, & Crystal, 2015;Zhou, Hohmann, & Crystal, 2012) to suggest that the memory contents that drive classically conditioned behavior come from a hierarchically structured record of the episodes in the conditioning experience.…”

“…Implications for content-based theories of Pavlovian conditioning. We take our results and those of others (Bratch et al, 2016;Crystal & Smith, 2014;Panoz-Brown et al, 2016;Panoz-Brown et al, 2018;Wilson, Mattell, & Crystal, 2015;Zhou, Hohmann, & Crystal, 2012) to suggest that the memory contents that drive classically conditioned behavior come from a hierarchically structured record of the episodes in the conditioning experience. The levels of the hierarchy are dictated by the different time spans at which the temporally structured conditioning experience unfolds-from point events (CS onsets and offsets and reinforcement deliveries), to the trial events in which these point events are embedded, to the sessions in which the trial events are embedded, to the epochs over which training may extend, in which the session events are embedded.…”

“…Consolidation and reconsolidation phenomena are plausibly considered manifestations of off-line stochastic model computation, because stochastic model development may lead to recoding memories so as to reduce the amount of memory required to preserve the same data (Dudai, 2012;Wang & Morris, 2010). The computation of stochastic models may also be the computational explanation for the replay of episodes during sleep and quiet wakefulness (Foster & Wilson, 2006;Jafarpour, Fuentemilla, Horner, Penny, & Duze, 2014;Mattar & Daw, 2018;Ólafsdóttir, Bush, & Barry, 2018;Panoz-Brown et al, 2018;Zentall, 2019).…”