Dissociation between recent and remote memory: a lesson from mutant mice with dimorphic cortical regions .-P31

The hippocampus plays a crucial role in the formation of novel spatial memories. It has been recently suggested that as these memories mature, they become dependent on extrahippocampal structures, such as the anterior cingulated cortex and the entorhinal cortex. In this study, we directly test this hypothesis by using a genetic animal model in which neocortical and archicortical regions are displaced. Cortical deletion of the orphan receptor chicken ovalbumin upstream promoter transcription factor (COUP-TFI) results in a massive expansion of the motor area (Armentanoet al., 2007;Tomassyet al., 2010). Here, we show that archicortical deletion of COUP-TFI results in a significant misplacement and volume reduction of the hippocampus and the entorhinal cortex, and in a miswiring of entorhinal cortical inputs to the hippocampus. Behavioral testing show that, despite the hippocampal defect, mutant mice are not impaired in the visible and hidden versions of the water maze if probed24 h after training (recent memory); on the contrary, they are strongly and selectively impaired in the spatial version of the task when tested 35 days after training (remote memory).Taken together, these findings suggest that the entorhinal-hippocampus input is not necessary to form novel spatial memories, but to maintain them for longer period