Serotonergic projections to the orbitofrontal and medial prefrontal cortices differentially modulate waiting for future rewards

Optogenetic activation of serotonergic neurons in the dorsal raphe nucleus (DRN) enhances patience when waiting for future rewards, and this effect is maximized by both high probability and high timing uncertainty of reward. Here, we explored which serotonin projection areas contribute to these effects using optogenetic axon terminal stimulation. We found that serotonin stimulation in the orbitofrontal cortex (OFC) is nearly as effective as that in the DRN for promoting waiting, while in the nucleus accumbens, it does not promote waiting. We also found that serotonin stimulation in the medial prefrontal cortex (mPFC) promotes waiting only when the timing of future rewards is uncertain. Our Bayesian decision model of waiting assumed that the OFC and mPFC calculate the posterior probability of reward delivery separately. These results suggest that serotonin in the mPFC affects evaluation of time committed, while serotonin in the OFC is responsible for overall valuation of delayed rewards.

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Reward-period Activity in Primate Dorsolateral Prefrontal and Orbitofrontal Neurons Is Affected by Reward Schedules

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2006.18.2.212 ◽

2006 ◽

Vol 18 (2) ◽

pp. 212-226 ◽

Cited By ~ 24

Author(s):

Satoe Ichihara-Takeda ◽

Shintaro Funahashi

Keyword(s):

Prefrontal Cortex ◽

Orbitofrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Onset Time ◽

Delayed Response ◽

Gradual Change ◽

Reward Schedule ◽

Motivational State ◽

Reward Delivery ◽

Dorsolateral Prefrontal

Reward-period activity observed in the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) is thought to represent the detection of reward delivery. To investigate whether this activity plays the same role in these areas, we examined this activity under different reward schedules and whether the reward schedule has similar effects on this activity in each of these areas. A monkey performed an oculomotor delayed-response (ODR) task under two reward schedules. In the ODR-1 schedule, the monkey received a large amount of reward only after four successful trials, whereas in the ODR-2 schedule, it received a small amount of reward after every successful trial. Although reward-period activity was observed in both areas, more neurons exhibited this activity in the OFC. Reward-period activity was modulated by the proximity to reward delivery in both areas and this feature was observed more frequently in the OFC. The onset time of this activity also gradually advanced depending on the proximity to reward delivery. Moreover, many OFC neurons with this activity responded to free reward delivery. These results indicate that reward-period activity in the OFC represents the detection of reward delivery and that the gradual change in the magnitude and the onset time of this activity represents the expectation of reward delivery. Similar features of reward-period activity were observed in DLPFC neurons, although a significant number of DLPFC neurons did not respond to free reward delivery and no advance was observed in the onset time of this activity. These results suggest that reward-period activity in the DLPFC participates in whether or not correct performance was achieved. Thus, although similar reward-period activity was observed in both areas, the activity in the OFC represents the detection of reward delivery and is affected by the monkey's motivational state, whereas that in the DLPFC seems to participate in monitoring whether or not the necessary performance is achieved.

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