Green and Swets, 1966; buy Capmatinib Histed et al., 2009). For each unit, we examined to what extent firing rates in fragments of 200 ms discriminated between S+ and S− by computing the shuffle-corrected ROC area, called Dcorrected ( Figure 3): an index ranging from 0 (no discriminative power) to 1/2 (maximum discriminative power; negative numbers incidentally occur because of limited sampling). We then averaged Dcorrected across units, while balancing, for a given rat, the number of cells entered in the analysis across pharmacological conditions. In the acquisition phase, D-AP5 caused a decrease in Dcorrected values for the odor period ( Figure 3; p < 0.01, Bootstrap

test with Bonferroni correction). In this phase, no significant drug effects were found in phases following odor sampling. In the reversal phase, D-AP5 significantly reduced Dcorrected values during the odor as well as early and late movement phases ( Figure S2). Units’ Dcorrected scores in the reversal phase may reflect

the sign (direction) of their acquisition-phase firing rate selectivity or a reversed selectivity. In fact, maintenance of cue selectivity across cue-outcome reversal has been linked to faster reversal learning ( Schoenbaum et al., 2007; Stalnaker et al., 2006). To assess the consistency of firing rate selectivity, we applied a sign function to the Dcorrected calculation. We found that, after reversal, firing rate selectivity was preserved especially Rigosertib manufacturer in the odor sampling phase of control, but not drug sessions, whereas firing rate selectivities showed a mixture of maintenance and flips for the movement and waiting phases ( Figures S3 and S4). The observed effects of D-AP5 all are unlikely to be a consequence of changes in the prevalence of firing-rate correlates. A unit was defined as having a firing-rate correlate for a given task period if its firing rate in that period differed significantly from the ITI firing rate. The distribution of firing rate correlates did not significantly differ between control and drug conditions across task periods

(Table 2; chi-square test; df = 4; p = 0.64). One route by which D-AP5 may impact discriminatory firing is through the impairment of NMDAR-dependent, long-term synaptic plasticity, which may be required for neurons to develop stimulus-outcome discrimination across learning trials. Alternatively, NMDARs may acutely support discriminatory firing because of their slow EPSP contributions. If the effects of D-AP5 are mediated via long-term plasticity, they should gradually become more pronounced across trials. To investigate how effects of D-AP5 on outcome-selective firing patterns develop across trials, we examined single-trial contributions to ROC discrimination scores using a leave-one-out procedure, yielding pseudo discrimination (PD) scores per trial (see Experimental Procedures).