NMDA‐receptor blockade by CPP impairs post‐training consolidation of a rapidly acquired spatial representation in rat hippocampus

Abstract

Recent evidence suggests that N-methyl-D-aspartate (NMDA)-receptor mediated plasticity in hippocampus has a more subtle role in memory-based behaviours than originally thought. One idea is that NMDA-based plasticity is essential for the consolidation of post-training memory but not for the initial encoding or for short-term memory. To further test this idea we used a three-phase variant of the hidden goal water maze task. In the first phase, rats were pre-trained to an initial location. Next, intense, massed training was done in a 2-h interval to teach the rats to go to a new location after either an injection of the NMDA receptor antagonist (6)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) or of vehicle. Finally, under drug-free conditions 24 h after new location training, a competition test was done between the original and new locations. We find that N-methyl-D-aspartate (NMDA)-receptor blockade has little or no effect on new location training. In contrast, when tested 24 h later, the strength of the trace for the new location learned during NMDA-receptor blockade was much weaker compared with the trace for the new location learned after saline injection. Further experiments showed similar effects when NMDA-receptors were blocked immediately after the new location training, suggesting that this is a memory consolidation effect. Our results therefore reinforce the notion that hippocampal NMDA-receptors participate in post-training memory consolidation but are not essential for the processes necessary to learn or retain navigational information in the short term.

Revealing Past Memories: Proactive Interference and Ketamine-Induced Memory Deficits

“…This suggests that the "strength" of the encoded representation is weakened under the influence of ketamine (Kentros et al, 1998). Studies have shown that posttraining administration of NMDA antagonists can disrupt retention or consolidation when administered after the acquisition of information (Packard and Teather, 1997;Santini et al, 2001;McDonald et al, 2005) (but see Day and Langston, 2006). We found no evidence that ketamine (50 -100 mg/kg) affected retention when the drug was administered after the sample.…”

The rodent hippocampus and spatial memory: from synapses to systems

“…209 for review] -although research to date has focused largely on the hippocampal side of the story. Consistent with this, the long-term retention of place memory (i.e., >24 h) is impaired by the blockade of NMDA receptor-dependent synaptic plasticity either before (see Synaptic plasticity and the rapid encoding of spatial information), or soon after, acquisition [210,211]. The latter finding suggests that the early stabilization of a memory requires additional offline episodes of NMDA receptor activation after the initial encoding event [see also refs.…”

Revisiting the cholinergic hypothesis in the development of Alzheimer's disease

“…A similar pattern of results is observed following complete lesions of the hippocampus. Previous studies have shown that rats with anterograde damage to the hippocampus are consistently impaired on the acquisition of the spatial version of the water maze (Morris et al, 1982;Sutherland et al, 1983;Ferbinteanu and McDonald, 2003;McDonald et al, 2005). Furthermore, rats with anterograde damage to the hippocampus are not impaired at either fear conditioning to cue or context; however, rats with damage to the hippocampus after training impairs retention of fear conditioning to context but not to cue (Phillips and LeDoux, 1992;Sanders et al, 2003;Wiltgen et al, 2006).…”