The role of D1-dopamine receptors in working memory-guided movements mediated by frontal cortical areas.

Abstract

Like the striatum, the frontal motor cortices receive dopaminergic fibers from midbrain dopamine cells and contain high levels of dopamine receptors. Among frontal cortical areas, the dorsolateral PFC (PFd1) and the dorsal premotor cortex (PMd) have strong neural connections and play a major role for working memory-guided directional movements. To reveal the role of dopamine in this cognitive motor function, dopamine antagonists (SCH23390 for D1 receptors and sulpiride for D2 receptors) were applied locally or iontophoretically to the PFd1 and PMd in monkeys that performed delayed-response tasks with memory-guided directional movements. Applications of SCH23390, but not sulpiride, to these areas had significant effects at both the behavioral and neuronal levels. In the PFd1 and at the behavioral level, local injections of SCH23390 induced specific errors for memory-guided saccades, whereas it had no effects on visually guided saccades. In the PMd, local injections of SCH23390 induced directional errors and increased reaction time and movement time in memory-guided reaching movements. At the neuron level, iontophoretic applications of SCH23390 attenuated directional tuning of neurons of the PFd1 and PMd, which showed directional activities during the delay-and/or response-period(s). These findings suggest that the activation of D1-dopamine receptors in these frontal cortical areas plays a facilitating role in a series of neuronal processes of working memory-guided directional movements; the working memory process for guiding motor act in the PFd1 and preparation/control of directional manual movements in the PMd. In addition, our findings may provide insight into symptoms of schizophrenia and Parkinson's disease; the dysfunction of D1-dopamine receptors in the PMd1 and PMd may contribute to some symptoms, such as bradyphrenia and bradykinesia, in these disorders.