For example, while the monkey performs a visual discrimination task, the noradrenergic neurons in the LC exhibit both phasic and tonic modes of firing, which are correlated with good and bad performance (Usher et al., 1999). Subsequent experiments showed that the phasic activity of LC neurons occurs specifically before the behavioral response, and it may serve to facilitate the task-related decision process (Clayton et al., 2004). In a study in the rat performing an odor-guided decision task, serotonergic neurons in the DRN showed transient firing precisely time locked to a variety of

task-related events (Ranade and Mainen, 2009). Another study in the monkey showed that firing rates Doxorubicin in vitro of the DRN neurons were modulated by both the expected and received reward sizes (Nakamura et al., 2008). Neurons in the primate basal forebrain are also modulated by novel or reinforced stimuli (Wilson and Rolls, 1990). In behaving rats, the noncholinergic basal forebrain neurons showed strong burst responses to

both reward- and punishment-predicting stimuli, and the occurrence of the burst is strongly correlated with successful sensory detection (Lin and Nicolelis, 2008). The neuromodulator especially linked to vigilance and attention is ACh. In the rat, behaviorally relevant sensory cues can evoke transient increases in ACh concentration in the prefrontal cortex at the time scale of seconds (Parikh et al., 2007), and activating cholinergic transmission in the prefrontal cortex improves the performance of a sustained attention task (St Peters et al., 2011). LDN-193189 clinical trial A recent study based on genetic manipulation with recombinant viral vectors in the prefrontal cortex further demonstrated the importance of nicotinic ACh receptors (nAChRs) in sustained attention

(Guillem et al., 2011). Cholinergic signaling is also involved in selective attention. In the monkey performing a top-down spatial attention task, local application of ACh in the primary visual cortex was found to enhance the attentional modulation of neuronal firing rates, whereas mAChR Mephenoxalone antagonist had the opposite effect (Herrero et al., 2008). Together, these studies indicate that in addition to the daily sleep-wake cycle, the subcortical neuromodulatory circuits also serve to regulate arousal and attention on a faster time scale. Numerous studies in monkeys performing selective attention tasks have shown increased neuronal responses (Reynolds and Chelazzi, 2004), which are thought to enhance the perceptual saliency of the attended stimuli. Recent studies have shown that attention also causes a decrease in stimulus-independent correlated firing between neurons (Cohen and Maunsell, 2009; Mitchell et al., 2009), which may improve sensory encoding at the ensemble level (Zohary et al., 1994).