A new mode beyond the inverted-U region of the dopaminergic modulation of the prefrontal cortex

It is well known that dopamine (DA) modulates, via D1 receptors, the activity of the dorsolateral prefrontal cortex (DLPFC) for working memory in monkey with an inverted-U shape profile. The activity of the DLPFC is moderate and D1 receptors in the DLPFC are activated rather modestly. We studied the circuit dynamics of the DLPFC for wider variation of the cortical extracellular DA concentration than usually considered. The model we used for the analysis and the simulation has simple network architecture, consisting of a pyramidal neuron unit and an inhibitory interneuron unit that are reciprocally connected. Nevertheless, the network dynamics shows an interesting and unpredictable behavior in the hyperdopaminergic region. In this region, the simulation shows the emergence of a new mode of the activity, which is characterized by the hyperactivity of the DLPFC and the hyperactivation of the D1 receptors. This mode of activity shows a marked contrast to the conventional activity mode in the inverted-U region. We term this new mode the ‘H mode’. In this study, we characterize the H mode and argue its relevance to psychopathology. r 2006 Elsevier B.V. All rights reserved.