Its time course was similar to the time course of the saccade latency and velocity. In particular, positive VP neurons changed Selleck INK 128 their activity quickly after the small-to-large reversal, but more slowly after the large-to-small reversal, similarly to the changes in saccade latency and velocity. This impression was supported by a statistical analysis: their activity on the second trial after the small-to-large reversal was not statistically different from the activity in the subsequent 10 trials (p = 0.51, Wilcoxon signed-rank test), whereas the activity on the second trial after the large-to-small reversal was statistically

different from the activity in the subsequent 10 trials (p = 0.008). We also examined the activity of VP neurons in two different periods: postcue and postreward Galunisertib purchase periods (Figure S3). The changes in the postcue activity (Figure S3A) were similar to the changes in the presaccadic activity, confirming that the VP neurons maintained their reward expectation information derived from the cue. The changes in the postreward activity were more complex (Figure S3B). Both positive and negative neurons changed their activity roughly in relation to the amount of the received reward. Thus, VP neurons did not encode reward prediction errors, unlike several groups of neurons that are involved in dopamine release (Hong and Hikosaka, 2008; Hong et al.,

2011; Matsumoto and Hikosaka, 2007) but are similar to neurons in the dorsal raphe nucleus including serotonin neurons (Nakamura et al., 2008). Our results so far showed that VP neurons encoded the expected reward value in a manner that was associated with behavioral measures of motivation. If these neurons truly have a causal role in generating motivation, then inactivating the VP

should abolish the effects of expected reward value on behavior. Crucially, inactivation should not interfere with the sensorimotor aspects of behavior (such as perceiving the target or executing the saccade), only with the ability to regulate behavior based on the expected value. To test the hypothesis, we locally inactivated the VP and Idoxuridine its surrounding regions by injecting a GABAA receptor agonist, muscimol (0.88–44 mM, 1–2 μl) while one monkey performed a reward-biased visually guided saccade task (Lauwereyns et al., 2002; see Experimental Procedures). We tested whether the changes in saccade latency based on reward expectation (hereafter called “reward-dependent saccade latency bias”) were changed by the muscimol-induced inactivation. We carried out 4 unilateral and 17 bilateral injection experiments in monkey H within the period of 84 days (Table 1). Figure 6A depicts the injection sites in the left hemisphere on the basis of the histological reconstruction. We confirmed that, in case of bilateral injections, muscimol was injected roughly at the mirror-symmetric position in the right hemisphere (data not shown).