Dopaminergic control of working memory and its relevance to schizophrenia: A circuit dynamics perspective

Department of Electrical and Electronics Engineering, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
Neuroscience (Impact Factor: 3.36). 05/2006; 139(1):153-71. DOI: 10.1016/j.neuroscience.2005.08.070
Source: PubMed


This article argues how dopamine controls working memory and how the dysregulation of the dopaminergic system is related to schizophrenia. In the dorsolateral prefrontal cortex, which is the principal part of the working memory system, recurrent excitation is subtly balanced with intracortical inhibition. A potent controller of the dorsolateral prefrontal cortical circuit is the mesocortical dopaminergic system. To understand the characteristics of the dopaminergic control of working memory, the stability of the circuit dynamics under the influence of dopamine has been studied. Recent computational studies suggest that the hyperdopaminergic state is usually stable but the hypodopaminergic state tends to be unstable. The stability also depends on the efficacy of the glutamatergic transmission in the corticomesencephalic projections to dopamine neurons. When this cortical feedback is hypoglutamatergic, the circuit of the dorsolateral prefrontal cortex tends to be unstable, such that a slight increase in dopamine releasability causes a catastrophic jump of the dorsolateral prefrontal cortex activity from a low to a high level. This may account for the seemingly paradoxical overactivation of the dorsolateral prefrontal cortex observed in schizophrenic patients. Given that dopamine transmission is abnormal in the brains of patients with schizophrenia and working memory deficit is a core dysfunction in schizophrenia, the concept of circuit stability would be useful not only for understanding the mechanisms of working memory processing but for developing therapeutic strategies to enhance cognitive functions in schizophrenia.

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    • "Additionally, previous research suggests a reciprocal relationship between prefrontal and striatal dopaminergic dysfunction in schizophrenia. A number of researchers have suggested that prefrontal dopaminergic dysfunction may partly be the result of dysregulated input from the midbrain dopamine system (Braver et al., 1999; Braver and Cohen, 2000; Tanaka, 2006). On the other hand, according to the tonic-phasic dopamine theory introduced by Grace (1991), when the tonic activity is low, stressful stimuli are not optimally regulated by the PFC, resulting in increased phasic dopamine release in the striatum. "
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