The Role of Dopamine in Frontal Motor Cortical Functions of Monkeys

Abstract

Like the striatum, the frontal motor cortices receive dopaminergic fibers from midbrain dopamine cells and contain high levels of dopamine receptors. To reveal the role of dopamine in the frontal cortical areas for controlling voluntary movements, we examined the effects of application of selective dopamine antagonists (SCH23390 for D1 receptors and sulpiride for D2 receptors) to the dorsolateral prefrontal cortex (PFC), dorsal premotor cortex (PMd) and motor cortex (MC) while monkeys performed memory-guided and visually guided response tasks requiring directional movements. Application of the D1-dopamine antagonist SCH23390 to these areas had a significant effect on both behavior and neuron activities. At the behavioral level, local injections of SCH23390 had different effects in the different frontal areas examined. In the dorsolateral PFC, local injection of SCH23390 induced errors and increased reaction time (from a visual go signal to movement onset) for memory-guided saccades, whereas it had no effects on visually guided saccades. In the PMd, SCH23390 induced errors and increased both reaction time and movement time (from movement onset to offset) for both memory-guided and visually guided reaching movements. Finally, in the MC, SCH23390 did not increase errors or reaction time, but did increase movement time for both the memory-guided and visually guided reaching movements. At the neuron level, iontophoretic application of SCH23390 decreased task-related activities, and also decreased directional tuning of the activities in all of the areas examined. These findings suggest that dopamine in the frontal motor cortices plays a role in facilitating a series of processes for voluntary movement via activation of D1-dopamine receptors: the working memory process for guiding movements in the PFC, preparation for and initiation of movements in the PMd, and execution of movements in the MC.