Molecular mechanisms in the DG and CA3 regulate the balance between differentiation and generalization during retrieval in a cue-degraded context

FACUNDO MORICI; GALLO FRANCISCO; DINKA PIROMALLI GIRADO; NOELIA V WEISSTAUB; MAGDALENA MIRANDA; CARLA NAVAS; PEDRO BEKINSCHTEIN

Carlos Paz

Congreso; XXXiV Congreso de la Sociedad Argentina de Neurociencias; 2019

Sociedad Argentina de Neurociencias

Because our environment is permanently evolving, it is crucial forepisodic memory to remember our previous experiences despite environmental changes.Computational models have suggested the existence of a pattern completionprocess by which networks could retrieve entire memories from partial ordegraded cues. The CA3 region of the hippocampus was proposed to mediate thiscomputation by the plastic enhancement of the recurrent collateral connectionsof CA3 neurons that were active during learning. In this work, we manipulatedthe amount of cues available during retrieval (test phase) in a spontaneousobject recognition task to investigate the function of CA3 NMDA-receptors(NMDAR) for pattern completion. We show that pharmacological intervention ofhippocampal CA3 NMDAR receptors impairs retrieval of the object location memoryonly when cues are degraded, while similar manipulations in the dentate gyrushave no effect. Moreover, while the context alone is enough o guide retrievalof the object memory under partial cues, antagonists of NMDAR in the test phaseprevent this retrieval. These findings suggest that NMDAR in CA3 are necessaryfor the retrieval of spatial memories when the amount of environmentalinformation is reduced, and that plastic changes in the dentate gyrus and CA3are important to define if behavioral pattern separation or pattern completionoccurs when exposed to a modified context.