, 2009, Guarraci and Kapp, 1999 and Matsumoto and Hikosaka, 2009). Since

the neurons with excitatory responses to aversive events were excited by rewarding GDC-0449 nmr events as well, they were presumed to encode motivational salience rather than motivational value (Matsumoto and Hikosaka, 2009). Based on these findings, it was proposed that dopamine neurons are not a homogeneous population and are divided into multiple groups encoding distinct signals suitable for different functions (Bromberg-Martin et al., 2010b). Consistent with the idea, the dopamine system is involved in multiple functions. Especially, dopamine released in the prefrontal cortex (PFC) has been implicated in cognitive processing rather than motivational functions (Nieoullon, 2002 and Robbins and Arnsten, 2009), including attentional selection (Crofts et al., 2001 and Robbins and Roberts, 2007), saccade target selection (Noudoost and Moore, 2011), and performance monitoring (Ullsperger, 2010 and Vezoli and Procyk, 2009). In particular, a prominent role in working memory has been established. Extracellular dopamine level increases in the dorsolateral prefrontal cortex (dlPFC) during working memory performance (Watanabe et al., 1997), and the blockade of dopamine D1 receptors in the dlPFC impairs working memory (Li and Mei,

1994, Sawaguchi and Goldman-Rakic, 1991 and Sawaguchi and Goldman-Rakic, 1994). An electrophysiological study in Ketanserin monkeys performing spatial working memory tasks also reported consistent data showing that the blockade of dopamine D1 receptors attenuates the spatially tuned persistent firing Ulixertinib nmr of dlPFC neurons (Williams and Goldman-Rakic, 1995). Dopamine is therefore essential to prefrontal cognitive functions. These findings have inspired hypotheses about what signals dopamine neurons might convey to the PFC to support these cognitive functions (Cohen et al., 2002 and Durstewitz et al., 2000). However, despite the wealth of studies demonstrating that dopamine neuron signals are related to reinforcement

and motivation, little is known about whether dopamine neurons convey signals suitable for promoting cognitive processing. In the present study, we aimed at identifying the signals carried by dopamine neurons when monkeys were engaged in a cognitive task. Specifically, we recorded single-unit activity from dopamine neurons in the ventral midbrain, including the SNc and VTA, while monkeys were performing a delayed matching-to-sample (DMS) task that required working memory and visual search. We found that the activity of dopamine neurons at different locations within the ventral midbrain reflected signals suitable for distinct roles in cognitive processing. We trained two monkeys (monkey F and monkey E) to perform a DMS task (Figure 1A). Each trial began with the presentation of a colored fixation point.