, 2007; Stalnaker et al., 2006). Here, we show that this maintenance of neuronal cue selectivity is NMDAR-dependent. Altogether, these results support the conclusion that NMDAR blockade renders firing patterns of OFC units less robust in their discriminatory capacity during task acquisition and reversal, which may compromise the efficiency of OFC signaling during learning. During acquisition, the discriminatory power of OFC neurons was strongly affected only in the

odor period (Figure 3A). At first sight, these findings contrast with the reproducibly reported coding of outcome expectancy parameters by OFC neurons during post-decisional

anticipation INCB024360 and processing of outcomes (O’Neill and Schultz, 2010; Schoenbaum et al., 1998, 1999; van Duuren et al., 2008). Because the present study combined recording with check details local intervention, it presents a strong case for an NMDAR-dependent mechanism in OFC for pre-decisional processing of stimulus information, coupled to the retrieval of odor-associated values predicting future outcome. Do NMDARs primarily support learning-related synaptic plasticity in OFC or are they of foremost importance in acute information processing due to their slow-EPSP contributions? We found that the firing discrimination score increased significantly with learning during S+ and S− odor sampling in control sessions (Figures 4A and 4B). On both S+ and S− trials, electrophysiological discrimination scores diverged between control and drug sessions with progressive learning, supporting the idea that learning-related plasticity of OFC firing patterns is reduced or lost with D-AP5 perfusion. Because the difference in discrimination scores between control and NMDAR blockade increased

as learning progressed, Rutecarpine the results suggest that OFC NMDARs are important for expressing long-term plasticity as underlying stimulus-outcome associative learning. Although our results do not prove that NMDA receptors mediate synaptic modifications within the OFC itself (because in theory they could also relay information acquired in afferent regions such as BLA; Groenewegen and Uylings, 2000; Mulder et al., 2003; Schoenbaum et al., 2003b), there are several indications that a mere relaying role can be considered unlikely. First, the NMDAR-mediated component of synaptic potentials in PFC is especially strong for recurrent, intracortical connections, not for excitatory inputs from afferent regions (Rotaru et al., 2011). Second, D-AP5 primarily affected OFC encoding during the cue period and much less so during the later trial periods of movement, waiting, and outcome.