Pharmacological intervention of hippocampal CA3 NMDA receptors impairs acquisition and long-term memory retrieval of spatial pattern completion task

Abstract

Pattern completion is the ability to retrieve complete information on the basis of incomplete retrieval cues. Although it has been demonstrated that this cognitive capacity depends on the NMDA receptors (NMDA-Rs) of the hippocampal CA3 region, the role played by these glutamatergic receptors in the pattern completion process has not yet been specified. In the present study, we investigated the function of the CA3 NMDA-Rs during the different memory stages (acquisition, memory consolidation, and retrieval) in a spatial pattern completion task (when some visual cues were removed from the environment) in comparison to a standard spatial water maze task (when all visual cues were available in the environment). Thus, we coupled a massed training with the injection of NMDA-receptor antagonist (AP5) into the CA3 subfield of the dorsal hippocampus of C57BL/6 mice. Our results show that NMDA-Rs are not implicated in a standard situation but are crucial during both acquisition and long-term memory retrieval in pattern completion. This work provides the first evidence of a specific role of CA3 NMDA-Rs during memory process involved in the reactivation of incomplete memory trace, particularly when the amount of environmental information available is strongly limited. © 2009 Cold Spring Harbor Laboratory Press.