The importance of serotonin for orbitofrontal function.

Area of Science:

• Neuroscience
• Behavioral Science

Background:

• The orbitofrontal cortex (OFC) receives significant serotonin (5-HT) input from the dorsal and median raphe nuclei.
• The OFC's reciprocal connections allow it to modulate its own 5-HT input and influence forebrain 5-HT levels.

Purpose of the Study:

• To review evidence implicating orbitofrontal 5-HT in behavioral adaptation to changing reward contingencies.
• To explore the role of OFC 5-HT in reward exploitation versus exploration.

Main Methods:

• Review of studies in rodents and primates using methods like localized 5,7-dihydroxytryptamine (5,7-DHT) infusions, peripheral drug treatments (PCA, PCPA), and chronic cold stress.
• Analysis of genetic variations in the 5-HT transporter.
• Behavioral experiments, including extinction of a two-pattern discrimination task in marmosets with reduced OFC 5-HT.

Main Results:

• Reductions in OFC 5-HT impair behavioral adaptation to changes in reward value.
• This impairment is not due to insensitivity to reward loss, as evidenced by normal extinction response rates.
• Animals with reduced OFC 5-HT fail to explore alternative stimuli during extinction.

Conclusions:

• Orbitofrontal 5-HT plays a critical role in adaptive decision-making, specifically in balancing exploitation of current rewards and exploration of alternatives.
• Electrophysiological data suggest dorsal raphe nucleus neurons encode future motivational outcomes, supporting the role of OFC 5-HT in guiding these choices.