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The idea that an NMDA receptor (NMDAR)-dependent long-term potentiation-like process in the hippocampus is the neural substrate for associative spatial learning and memory has proved to be extremely popular and influential. However, we recently reported that mice lacking NMDARs in dentate gyrus and CA1 hippocampal subfields (GluN1(ΔDGCA1) mice) acquired the open field, spatial reference memory watermaze task as well as controls, a result that directly challenges this view. Here, we show that GluN1(ΔDGCA1) mice were not impaired during acquisition of a spatial discrimination watermaze task, during which mice had to choose between two visually identical beacons, based on extramaze spatial cues, when all trials started at locations equidistant between the two beacons. They were subsequently impaired on test trials starting from close to the decoy beacon, conducted post-acquisition. GluN1(ΔDGCA1) mice were also impaired during reversal of this spatial discrimination. Thus, contrary to the widely held belief, hippocampal NMDARs are not required for encoding associative, long-term spatial memories. Instead, hippocampal NMDARs, particularly in CA1, act as part of a comparator system to detect and resolve conflicts arising when two competing, behavioural response options are evoked concurrently, through activation of a behavioural inhibition system. These results have important implications for current theories of hippocampal function.

Original publication

DOI

10.1098/rstb.2013.0149

Type

Journal article

Journal

Philos Trans R Soc Lond B Biol Sci

Publication Date

05/01/2014

Volume

369

Keywords

NMDAR, hippocampus, long-term potentiation, spatial learning, synaptic plasticity, watermaze, Animals, Discrimination Learning, Hippocampus, Long-Term Potentiation, Maze Learning, Memory, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Receptors, N-Methyl-D-Aspartate, Spatial Behavior