Hippocampal NMDA receptors are important for behavioural inhibition but not for encoding associative spatial memories

摘要

The idea that anNMDAreceptor (NMDAR)-dependent long-termpotentiationlike process in the hippocampus is the neural substrate for associative spatial learning andmemory has proved to be extremely popular and influential.However, we recently reported that mice lackingNMDARs in dentate gyrus andCA1 hippocampal subfields (GluN~(?DDGCA1) mice) acquired the open field, spatial reference memorywatermaze task aswell as controls, a result that directly challenges this view. Here, we show that GluN~(?DDGCA1) 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. GluN~(?DDGCA1) mice were also impaired during reversal of this spatial discrimination. Thus, contrary to the widely held belief, hippocampalNMDARs are not required for encoding associative, long-termspatialmemories. Instead, hippocampalNMDARs, particularly in CA1, act as part of a comparator systemto 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.