Opaminergic Control of Working Memory Nd Its Relevance to Schizophrenia: a Circuit Ynamics Perspective

bstract—This article argues how dopamine controls workng memory and how the dysregulation of the dopaminergic ystem is related to schizophrenia. In the dorsolateral prerontal cortex, which is the principal part of the working emory system, recurrent excitation is subtly balanced with ntracortical inhibition. A potent controller of the dorsolateral refrontal cortical circuit is the mesocortical dopaminergic ystem. To understand the characteristics of the dopamineric control of working memory, the stability of the circuit ynamics under the influence of dopamine has been studied. ecent computational studies suggest that the hyperdopainergic state is usually stable but the hypodopaminergic tate tends to be unstable. The stability also depends on the fficacy of the glutamatergic transmission in the corticomesncephalic projections to dopamine neurons. When this corical feedback is hypoglutamatergic, the circuit of the dorsoateral prefrontal cortex tends to be unstable, such that a light increase in dopamine releasability causes a catatrophic jump of the dorsolateral prefrontal cortex activity rom a low to a high level. This may account for the seemingly aradoxical overactivation of the dorsolateral prefrontal corex observed in schizophrenic patients. Given that dopamine ransmission is abnormal in the brains of patients with chizophrenia and working memory deficit is a core dysfuncion in schizophrenia, the concept of circuit stability would be seful not only for understanding the mechanisms of workng memory processing but for developing therapeutic stratgies to enhance cognitive functions in schizophrenia. 2005 IBRO. Published by Elsevier Ltd. All rights reserved.