The, ventral striatum (VS) is a dopamine rich deep brain structure involved in the processing of reward. After damage to this structure animals and humans have difficulties in reacting properly to reward;such individuals often become apathetic and are not motivated to carry out normal behavioral tasks. Many observations suggest that the ventral striatum is implicated in severe behavioral disorders such as depression and addiction. Neurons in the ventral striatum of monkeys are known to encode information related to reward. We are studying the role of the by recording single unit neuronal activity monkeys while they engage in simple choice task in which they are presented with different valued predicted outcomes. In this task, a visual cue presented at the beginning of a trial indicates both the reward size and delay if the trial is completed successfully. The value of the outcome is manipulated by changing the amount of juice and the delay to reward after a choice is made. Monkeys predictably accepted high value trials, that is, trials with large reward and short delays, and skipped low value trials, that is, trials with small rewards and long delays. In the past it has been suggested that these two variables are encoded by different neurons. In the ventral striatum there are two types of neurons, so-called phasically active neurons (PANs,putative medium spiny GABAergic projection neurons) that increase their firing when events such as cue appearance or reward delivery, and tonically active neurons (TANs putative aspiny cholinergic interneurons) that fire continually at a low rate, and the rate is briefly modulated when a significant event occurs. We identified 88 PANs and 43 TANs (see Figure 3 for examples). Overall 66/131 (50%) neurons demonstrated significant effects of reward size or delay on the firing rate following cue presentation. Significant main effects were seen for size alone in 32 neurons (24%), delay alone in 9 neurons (7%), and both size and delay in 25 neurons (19%). A significant interaction effect of size and delay was seen in 23 neurons (18%). Among PANs, the effects for size alone and both size and delay were seen more than for delay alone (24/88 (27%) size alone, 3/88 (3%) delay alone, 18/88 (20%) both size and delay). Most TANs showed the burst-pause-burst pattern elicited by reward predicting stimuli seen in TANs by others in the past. Following cue presentation, 18/43 (42%), 7/43 (16%), and 5/43 (12%) neurons showed significant main effects on firing rate of both reward size and delay, reward size alone, and reward delay alone, respectively. Following reward delivery, 4/43 (9%), 4/43 (9%), and 4/43 (9%) neurons showed a significant main effect on firing rate of both reward size and delay, reward size alone, and reward delay alone, respectively. Interaction effects of reward size and reward delay were seen following cue presentation and reward delivery in 16/43 (37%) and 6/43 (14%) neurons, respectively. Thus, both tonically active neurons and phasically active neurons in ventral striatum show responses. However, PANs seem primarily sensitive to reward size whereas PANs are sensitive to both. Although the central noradrenergic system is more classically associated with arousal, attention or cognitive flexibility, several recent show that the noradrenergic system also has a central role in normal motivated activity. We compared the responses of dopaminergic and noradrenergic neurons around the time of major task events, visual cues predicting trial outcome and operant action to complete a trial. The responses of the two type of neurons were similar in that they occurred at the same time. They were also similar in that they both responded most strongly to the first cues in schedules, which are the most informative cues. The neuronal responses around the time of the monkeys'actions were different, in that the response intensity profiles changed in opposite directions. Dopaminergic responses were stronger around predictably rewarded correct actions whereas noradrenergic responses were greater around predictably unrewarded correct actions. The complementary response profiles related to the monkeys operant actions suggest that DA neurons might relate to the value of the current action whereas the noradrenergic neurons relate to the psychological cost of that action.that the role of the noradrenergic system would be complementary to that of the dopaminergic system, in that it would promote behavioral responses associated with greater efforts, rather than greater value as it seems to be the case for dopaminergic neurons. To study the activity of LC neurons further, we are recording single unit activity to explore the influence of several parameters including the size of the expected reward, the behavioral state (thirst), and whether or not the monkey had to make a action to obtain the reward. We relate LC activity to two behavioral measures of the subjective reward value: lipping, an appetitive Pavlovian reflex and bar release, a goal directed action. As we saw previously, LC responses to the cue at the trial onset increased with the value of the expected reward. Later in the trial, when monkeys initiated a bar release, the magnitude of the associated LC activation decreased with as the value of the expected reward increased. We speculate that LC neurons encode the amount of subjective effort needed to trigger the action in the face of a relatively small reward. These results support our hypothesis. Overall, we propose that LC neuronal activity reflects the level of energy needed to induce an action when the current reward value is in itself not large enough, that is, the LC neurons supply the increment needed to reach the threshold for action when the incentive for reward is not currently enough. A corollary of this is only an immediately imminent reward provides enough impetis to activate an action and that the noradreline neurons must be activated for action to occur when the reward is discounted by either time, or intrinsic value such as size. Thus, the noradrenergic system would play a key role in motivation and complement the well-established contribution of the dopaminergic system.

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