Figure 13.

(A) Graphical representation of the relationship between D1R stimulation and pyramidal cell activity (green) or WM performance (black). Different levels of D1R stimulation are indicated by numbers on the x-axis. Point 1 represents no D1R stimulation, resulting in very little pyramidal cell output and poor WM performance. Point 2 represents low levels of D1R stimulation, with strong pyramidal cell activity but with suboptimal WM performance. Point 3 represents moderate levels of D1R stimulation. At this point, pyramidal cell activity is lower, but WM performance is optimal. Finally, point 4 represents high levels of D1R stimulation, and both pyramidal cell activity and WM performance are diminished. Note that although both pyramidal cell activity and WM performance have inverted-U relationships with D1R activation, the cell activity peak is left shifted compared with WM performance. (B) Simplified circuit model of the relationship between CR interneurons (red), PV interneurons (blue), and pyramidal cells (green). Panel 1 represents activity levels with there is no D1R stimulation. Panel 2 represents cellular activity levels at low D1R stimulation. D₅ receptors on CR interneurons would be preferentially activated, enhancing their output, resulting in decreased PV interneuron activity, and disinhibiting the pyramidal cell. Panel 3 represents cellular activity levels at moderate D1R stimulation. Whereas D₅ receptors on CR interneurons are still being activated, D₁ receptors on PV interneurons are also now stimulated, allowing the PV interneurons to overcome some of the inhibition by CR interneurons which in turn results in decreased pyramidal cell activity. Finally, panel 4 represents cellular activity levels at high D1R stimulation. D₁ receptors on the PV interneurons are now maximally stimulated, overriding most of the inhibition from CR interneurons. PV interneuron activity will be greatly enhanced, resulting in a dramatic reduction in pyramidal cell output.