Abstract
Pattern completion, the ability to retrieve complete memories initiated by subsets of external cues, has been a major focus of many computation models. A previously study reports that such pattern completion requires NMDA receptors in the hippocampus. However, such a claim was derived from a non-inducible gene knockout experiment in which the NMDA receptors were absent throughout all stages of memory processes as well as animal's adult life. This raises the critical question regarding whether the previously described results were truly resulting from the requirement of the NMDA receptors in retrieval. Here, we have examined the role of the NMDA receptors in pattern completion via inducible knockout of NMDA receptors limited to the memory retrieval stage. By using two independent mouse lines, we found that inducible knockout mice, lacking NMDA receptor in either forebrain or hippocampus CA1 region at the time of memory retrieval, exhibited normal recall of associative spatial reference memory regardless of whether retrievals took place under full-cue or partial-cue conditions. Moreover, systemic antagonism of NMDA receptor during retention tests also had no effect on full-cue or partial-cue recall of spatial water maze memories. Thus, both genetic and pharmacological experiments collectively demonstrate that pattern completion during spatial associative memory recall does not require the NMDA receptor in the hippocampus or forebrain.
Highlights
Memory retrieval is a rapid reconstructive process involving a recapitulation of the previously acquired information [1,2,3]
On its face value, seems to provide the only experimental evidence for the role of the NMDA receptor in pattern completion during associative memory recall, it carries a significant caveat because the gene knockout used in that study lacked inducible temporal controls, and as a result, the NMDA receptor was absent in all stages of memory processes [8]
To avoid any disruption in learning and consolidation, we feed the mice with normal food and trained both inducible and CA1specific NR1 knockout mice (iCA1-KO) and their control littermates in the hiddenplatform water maze task with four prominent, distal visual cues hung on the surrounding black curtain
Summary
Memory retrieval is a rapid reconstructive process involving a recapitulation of the previously acquired information [1,2,3]. Since the NMDA receptor channel has a longer openingduration, it has been speculated by computational biologists that the NMDA receptor might be a candidate molecule for initiating pattern completion within the auto-associative memory network during memory retrieval. In line with such a speculation, a previous study reports that CA3-specific NMDA receptor knockout mice exhibited performance deficits during the recall of spatial reference memory under the partial cue condition [8]. This pattern completion deficit during recall may lead to a false interpretation that the NMDA receptor in the hippocampus is required for associative memory recall [8]
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