A neurocomputational theory of the dopaminergic modulation of working memory functions

The dopaminergic modulation of neural activity in the prefrontal cortex (PF C) is essential for working memory. Delay-activity in the PFC in working me mory tasks persists even if interfering stimuli intervene between the prese ntation of the sample and the target stimulus. Here, the hypothesis is put forward that the functional role of dopamine in working memory processing i s to stabilize active neural representations in the PFC network and thereby to protect goal-related delay-activity against interfering stimuli. To tes t this hypothesis, we examined the reported dopamine-induced changes in sev eral biophysical properties of PFC neurons to determine whether they could fulfill this function. An attractor network model consisting of model neuro ns was devised in which the empirically observed effects of dopamine on syn aptic and voltage-gated membrane conductances could be represented in a bio physically realistic manner. In the model, the dopamine-induced enhancement of the persistent Na+ and reduction of the slowly inactivating K+ current increased firing of the delay-active neurons, thereby increasing inhibitory feedback and thus reducing activity of the "background" neurons. Furthermo re, the dopamine-induced reduction of EPSP sizes and a dendritic Ca2+ curre nt diminished the impact of intervening stimuli on current network activity . In this manner, dopaminergic effects indeed acted to stabilize current de lay-activity Working memory deficits observed after supranormal D1-receptor stimulation could also be explained within this framework. Thus, the model offers a mechanistic explanation for the behavioral deficits observed afte r blockade or after supranormal stimulation of dopamine receptors in the PF C and, in addition, makes some specific empirical predictions.