Fig. 7.

Theoretical implications of a bidirectional change in inhibition in the PFC. Left, In state 1, the D2 modulation predominates, and there is a net reduction in inhibition. As a result, multiple inputs impinging on the PFC have access to the working memory buffers, allowing multiple representations (i.e., sustained activity driven by recurrent excitation that encodes working memory information) to be held in PFC networks nearly simultaneously.Right, In state 2, the D1 modulation predominates, and there is a net increase in inhibition. As a result, inputs have difficulty accessing PFC networks. However, particularly strong inputs, which can overcome the effects of heightened inhibition, benefit from the simultaneous D1-mediated increases in long-lasting inward currents (i.e., persistent Na⁺ and NMDA currents), which produce very active and stable network representations, even after the offset of the initiating stimulus (Yang and Seamans, 1996; Durstewitz et al., 2000; Seamans et al., 2001). In this way, dopamine may first allow an exploration of the input space (state 1), entertaining multiple network representations nearly simultaneously. Subsequent transition into state 2 shuts off the influence of weak inputs on PFC networks and strongly stabilizes one or a limited set of representations, which would then have complete control of PFC output.