Stable and Unstable Activation of the Prefrontal Cortex with Dopaminergic Modulation
The so-called inverted-U shaped profile of the dependence of working memory performance on D1 receptor activation in the prefrontal cortex (PFC) illustrates how the cognitive function declines with the deviation of the dopamine (DA) level in the PFC from the optimum point. A recent computational study, however, suggests that the PFC circuit is not always stable along the inverted-U shaped curve. This is due to effectively positive feedback control of the prefronto-mesoprefrontal system under hypodopaminergic conditions. The instability of the PFC circuit makes the activity of the PFC largely fluctuating. Because of this, even a slight increase in DA releasability causes a catastrophic jump of the activity of the PFC from a low to a high level. Under hyperdopaminergic conditions, in contrast, the PFC circuit is stable by means of negative feedback control. This chapter reviews these computational studies and argues the stable and unstable activation of the PFC in connection with cognitive deficits observed in schizophrenia.
KeywordsPrefrontal Cortex Pyramidal Neuron Work Memory Performance Stable Fixed Point Unstable Fixed Point
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