Dissecting Spatial Knowledge from Spatial Choice by Hippocampal NMDA Receptor Deletion

Hippocampal NMDA receptors (NMDARs) and NMDAR-dependent synaptic plasticity are widely considered as crucial substrates of long-term spatial memory, although their precise role remains uncertain. Here we show that GluN1(ΔDGCA1) mice, lacking NMDARs in all dentate gyrus and dorsal CA1 principal cells, acquired the spatial reference memory watermaze task as well as Controls, despite impairments on the spatial reference memory radial maze task. In a novel spatial discrimination watermaze paradigm, using two visually identical beacons, GluN1(ΔDGCA1) mice were impaired at using spatial information to inhibit selecting the decoy beacon, despite knowing the platform’s actual spatial location. This failure could suffice to impair radial maze performance despite spatial memory itself being normal. Thus, these hippocampal NMDARs are not essential for encoding or storing long-term, associative spatial memories. Instead, we demonstrate an important role for the hippocampus in using spatial knowledge to select between alternative responses that arise from competing or overlapping memories.