05). Figure 5D shows the average deflection (n = 11,330 deflections, 28 electrodes from five sessions) and the power spectrum of the LFP trace over 400 ms windows centered on each deflection (100 ms before to 300 ms after the initial sharp voltage change). It revealed a large peak at alpha frequencies (12.2 Hz) and, indeed, the power spectra of the LFPs during strong deflection episodes showed a marked increase in alpha oscillations (∼12 Hz) (see Figure S4 for an example). We compared LFP oscillatory power on correct trials during baseline blocks with the postinjection blocks separately

for sessions or recording sites with and without deflections. In baseline blocks, there was a prominent alpha/beta band (10–30 Hz) during the fixation, delay, and saccade execution epochs (Figures 6A and 6B). During postinjection blocks after injection MK-8776 price of SCH23390 (n = 163 electrodes), but not saline (n = 84 electrodes), there was an increase in the power of oscillations

below 30 Hz compared to baseline blocks. The deflections have an alpha component (see above) so, naturally, sites with deflections (n = 95) showed an increase in alpha band (10–14 Hz) after SCH23390 and also in beta band (14–30 Hz) for novel and familiar associations over baseline blocks (Figures 6A and 6B, Wilcoxon test, p < 0.05, shaded areas; Figure 6C, last 20 trials/block). see more Importantly, this increase in low-frequency power in the LFPs was still observed in sites without deflections (n = 68, Figure 6B), indicating that the SCH23390-induced increase in low-frequency oscillations was not due to the deflections alone. This increase was more pronounced for novel than familiar associations in only sites without deflections (Figures 6B and 6C; Wilcoxon test, p < 0.05). The increase in alpha/beta oscillations was also observed in sessions without deflections on any recording site (Figure S5)

and was greater at sites where blockade of D1Rs impaired learning compared to areas where learning was intact (Figure S5). Our findings indicate that dopamine D1 receptors in the monkey lateral PFC are likely to be involved in learning new cue-response associations but less involved in performance of familiar associations. After the injection of a D1R antagonist, especially in the ventrolateral PFC, monkeys learned new cue-response associations much more slowly, whereas performance of highly familiar associations was intact. Two not mutually exclusive possibilities may account for this dissociation: (1) familiar associations are not dependent on prefrontal D1Rs, and (2) they are dependent on another brain area, such as the striatum, where they could be encoded as habits (Graybiel, 2008).