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.
RESUMOA crescente prevalência de diabetes mellitus (DM) em países em desenvolvimento, associada à facilidade de se identificar indivíduos de alto risco para a doença, tornam interessante a idéia de se introduzir medidas que visem à prevenção da doença. Vários estudos comprovam os benefícios de mudanças no estilo de vida em prevenir ou retardar a progressão da tolerância à glicose diminuída para o DM. A revisão destes estudos mostra que é possível reduzir em 50 a 60% a incidência de DM intervindo-se no estilo de vida destes indivíduos, resultado superior ao obtido naqueles que, até o momento, utilizaram medidas farmacológi-cas com o mesmo objetivo. Apesar da eficácia destas simples medidas de prevenção por meio de mudanças no estilo de vida, estas são de difícil aderência e implementação em comunidades. Em nosso meio, são necessários estudos para avaliar as dificuldades de se implantar um programa nacional de prevenção de DM e outras doenças relacionadas ao estilo de vida em brasileiros de alto risco. Considering the increasing prevalence of diabetes mellitus (DM) in underdeveloped countries as well as the simplicity of identifying individuals at high risk for such disease, implementation of intervention measures for its prevention is of great interest. Several studies have confirmed the benefits of lifestyle changes in preventing or postponig the progression from impaired glucose tolerance to DM. The review of these studies showed a 50% to 60% reduction in the incidence of DM by means of lifestyle modifications. Such results are better than those reported in studies in which pharmacological interventions were used with the same purpose. Despite the efficacy of lifestyle changes for the prevention of DM, compliance may represent a limitation to be implemented in communities. In our country, studies are necessary to assess the barriers for the implementation of a population-based program for the prevention of DM and other lifestyle related diseases in high-risk Brazilian subjects.
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