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Behavioral, molecular and neuronal mechanisms involved in recognition memory retrieval under degraded spatial cues in the rat hippocampus

M. Miranda,Azul Silva,J. F. Morici,M. A. Coletti,M. Belluscio,P. Bekinschtein

Published 2023 in bioRxiv

ABSTRACT

In a constantly changing environment, organisms face the challenge of adapting their behavior by retrieving previous experiences or acquiring new information. Previous research has postulated that this balance between memory generalization and differentiation manifests in a dichotomic manner. When environmental information exceeds a given threshold, activation of a stored representation could initiate retrieval, but below this threshold, a novel event could be encoded with a concomitant remapping of the internal representation in the hippocampus. Here, we examined the hippocampal molecular and neuronal mechanisms underlying retrieval in a cue-degraded environment by combining in vivo electrophysiological recordings and pharmacological manipulations. We developed a memory recognition task that allows a graded decrease in the contextual cues present during retrieval. We found that the manipulation of the number of visual cues was consistent with the activation or not of the contextual memory trace. Retrieval of a specific context memory was reflected by the level of CA3 remapping, demonstrating a clear relationship between remapping and contextual recognition. Also, manipulation of NMDAR activity in the DG-CA3 circuit bidirectionally modulated contextual memory retrieval. The blockade of NMDAR in CA3 impaired recognition in a cue-degraded, but not in a full-cue context, while their activation has the opposite effect. Conversely, blockade of NMDAR in the DG promoted retrieval under an even more cue-degraded environment, while activation had the opposite effect. Our results provide evidence for a flexible interaction between environmental cues and information stored in the hippocampus and give new insights into the biological mechanisms that balance memory encoding and retrieval.

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