Learning in the absence of experience-dependent regulation of NMDAR composition

Olfactory discrimination (OD) learning consists of two phases: an initial N-methyl-D-aspartate (NMDA) receptor-sensitive rule-learning phase, followed by an NMDA receptor (NMDAR)-insensitive pair-learning phase. The rule-learning phase is accompanied by changes in the composition and function of NMDARs at synapses in the piriform cortex, resulting in a high level of the NR2a subunit relative to NR2b. Here we show that the learning-induced changes in NMDAR composition in the adult piriform cortex are due to a decrease in the level of the NR2b subunit protein, rather than an increase in the level of NR2a. Chronic administration of an NMDAR open channel blocker during training delays OD learning and blocks learning-induced changes in NMDAR subunit composition. However, the animals still learn the OD task. Our data demonstrate that learning can occur in the absence of activity-dependent regulation of NMDAR composition, suggesting differences in the mechanism for long-term maintenance of NMDAR-dependent and NMDAR-independent learning.