The role of CA3 hippocampal NMDA receptors in paired associate learning

The hippocampus is necessary for declarative memory in humans and episodic memory in rodents. Considerable current research is focused on the role of plasticity within specific subfields of the hippocampus. Here, using a viral vector to temporally control a focal deletion of the NR1 gene, we show that learning novel paired associations between specific cues and their context is dependent on CA3 NMDA receptors. Deletion of CA3 NR1 genes in < 30% of the dorsal hippocampus was sufficient to disrupt new learning, whereas the same treatment does not prevent expression of previously acquired paired associates and does not affect the ability to discriminate contexts or paired associate learning when either the cues or the context is familiar. The findings suggest that CA3 NMDA receptors specifically support the encoding of new experiences to involve incidental and contingent associations.