NMDA receptors control cue-outcome selectivity and plasticity of orbitofrontal firing patterns during associative stimulus-reward learning.

Neural activity in orbitofrontal cortex has been linked to flexible representations of stimulus-outcome associations. Such value representations are known to emerge with learning, but the neural mechanisms supporting this phenomenon are not well understood. Here, we provide evidence for a causal role for NMDA receptors (NMDARs) in mediating spike pattern discriminability, neural plasticity, and rhythmic synchronization in relation to evaluative stimulus processing and decision making. Using tetrodes, single-unit spike trains and local field potentials were recorded during local, unilateral perfusion of an NMDAR blocker in rat OFC. In the absence of behavioral effects, NMDAR blockade severely hampered outcome-selective spike pattern formation to olfactory cues, relative to control perfusions. Moreover, NMDAR blockade shifted local rhythmic synchronization to higher frequencies and degraded its linkage to stimulus-outcome selective coding. These results demonstrate the importance of NMDARs for cue-outcome associative coding in OFC during learning and illustrate how NMDAR blockade disrupts network dynamics.