, 2007; Robbins and Everitt, 1996; Wise, 1996). The VP receives GABAergic projections from the VS and, in turn, projects to many brain areas involved in control of motivation such as the ventral tegmental area (VTA), substantia nigra pars

compacta (SNc), and pars reticulata (SNr), thalamic mediodorsal nucleus (MD), and lateral habenula (LHb) (Haber and Knutson, 2010; Humphries and Prescott, 2010). We chose the VP as a first step to answer the question, because its activity should be more directly correlated with changes in the animal’s performance due to the close connectivity between the VP and motor output regions. It has been suggested that the VP may serve as a “limbic final common pathway” for processing of reward (Smith et al., 2009). In Pavlovian tasks, KU-55933 in vitro neurons in the rat VP responded to sensory stimuli that predicted an upcoming reward as well as to the reward itself (Smith et al., 2011; Tindell et al., 2004). Lesions, inactivations, and chemical manipulations of the rodent VP enhance or suppress Erastin reward-seeking behaviors (Cromwell and Berridge, 1993; Farrar et al., 2008; Johnson et al., 1996; McAlonan et al., 1993;

Smith and Berridge, 2005). Chemical activation of the monkey VP by local bicuculline injection induced stereotyped, non-purposive behavior (Grabli et al., 2004). In humans, bilateral lesions of the globus pallidus (GP) and the VP lead to a lack of motivation and pleasure (Bhatia and Marsden, 1994; Miller et al., 2006). Recent human imaging studies have demonstrated that the VP is activated during various kinds of motivational tasks associated with the primary (food and waters) and secondary (monetary gains) reward (Beaver et al., 2006; Pessiglione Oxalosuccinic acid et al., 2007). However, few studies have examined how individual VP neurons encode motivational/emotional states (Ito and Doya, 2009; Smith et al., 2011; Tindell

et al., 2004) and how they modulate goal-directed behavior. In our experiments we manipulated the value of an upcoming action by asking two macaque monkeys to perform a reward-biased saccade task. We found that many VP neurons showed differential activity encoding expected reward values. The role of the VP neuronal activity in motivating or demotivating the goal-directed saccade was supported by chemical inactivations of the VP in one of the monkeys. To examine the functional roles of the VP in reward-oriented actions, we recorded activity of single neurons in the VP while two monkeys (P and H) were performing a reward-biased memory-guided saccade task (Ding and Hikosaka, 2006; Kawagoe et al., 1998; Nakamura et al., 2008), in which reward size was associated with the direction of saccade (Figures 1A and 1B). A trial started with the appearance of a central point that the monkey had to fixate.