Differential changes in glutamate concentration in the primate prefrontal cortex during spatial delayed alternation...

Glutamate is a major neurotransmitter in the mammalian brain and glutamatergic neurotransmission in the frontal cortex is indicated to play important roles in cognitive operations. We previously examined changes in extracellular dopamine in the primate frontal cortex in cognitive tasks, and in this paper we extend this to glutamate. We employed, as cognitive tasks, a delayed alternation task where the animal must retain information in working memory, and a sensory-guided task in which there is no working memory requirement but there may be more sensory processing requirements. Using the in vivo microdialysis method, we examined changes in extracellular glutamate concentration in the dorsolateral, arcuate, orbitofrontal, and premotor areas of the primate frontal cortex. Compared to basal rest levels, we observed significant increases in glutamate concentration in dorsolateral and arcuate areas of the prefrontal cortex during the sensory-guided task, but did not find significant changes in any of the frontal areas examined during the delayed alternation task. When glutamate concentration was compared between the delayed alternation and sensory-guided tasks, difference was observed only in the dorsolateral prefrontal cortex, especially in the ventral lip area of the principal sulcus. The results indicate the importance of glutamate in processing sensory information but not in retaining information in working memory in the primate dorsolateral and arcuate prefrontal cortex. We also compared the concentration of glutamate and dopamine in the tasks. We found a double dissociation in the concentration of glutamate and dopamine in the dorsolateral area: there was an increase in glutamate but no change in dopamine during the sensory-guided task, whereas there was an increase in dopamine but no change in glutamate during the delayed alternation task. It is thus suggested that in the primate dorsolateral prefrontal cortex, increased glutamate tone without dopamine increase facilitates sensory-guided task performance, while increased dopamine tone without glutamate increase is beneficial for working memory task performance.