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Durstewitz, Daniel Dopamine Modulation of Prefrontal Cortex II: Computational Network Model Dopamine (DA) plays an important role in working memory and influences multiple intrinsic ionic and synaptic currents of PFC neurons. However, it is unclear how the DA- induced cellular changes relate to the role of DA in working memory. Recently we proposed that DA might enable PFC networks to sustain task-related activity even in the presence of interfering stimulation. Here, we extend these studies by investigating how DA affects activity states in a network model of highly realistic PFC compartmental model neurons, incorporating recent in vitro findings (Seamans et al., PFC I). Pyramidal model neurons reproduced whole-cell recordings from the soma and dendrites of PFC layer V pyramidal cells and were combined with compartmental models of GABAergic interneurons in a small PFC model network. A 'DA condition' was defined in the model relative to a 'baseline' state by shifting DA-modulated parameters of NMDA and GABAA synaptic currents, and of INAP, ICaN, and IKS intrinsic currents according to recent in vitro data and as outlined in Seamans et al. (PFC I). In the simulated network, DA suppressed low frequency, spontaneous firing driven by background synaptic inputs while it strongly enhanced a high activity state elicited by a short, strong stimulus and sustained by recurrent excitation. In the DA condition, it was more difficult to disrupt ongoing activity patterns, which were sustained for longer periods of time. On the other hand, in the baseline condition, it was easier to evoke activity patterns, which sometimes 'popped out' spontaneously. This suggests that low prefrontal DA favors variability by allowing many different activity patterns to sweep through PFC circuits, whereas high DA focuses on and stabilizes a limited number of neural representations relevant to the present task context.
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