Fig. 1.
Dynamic network connectivity in the dorsolateral prefrontal cortex (PFC) [adapted from Arnsten and colleagues [15••]]. The neuromodulators norepinephrine and dopamine mediate the strength of the network, residing in the dorsolateral PFC, that underlies working-memory ability. On the left (green) side of the figure, the binding of norepinephrine (represented by the orange triangles) to its receptor (α2A) strengthens the network by inhibiting the release of cyclic adenosine monophosphate (cAMP), which results in uninterrupted cognitive function. Conversely, on the right (red) side of the figure, the binding of dopamine to its receptor (D1) results in increased adenylyl cyclase (AC) activity via the activation of stimulatory G-protein (Gs). Increased AC activity results in enhanced cAMP concentration, and this results in the opening of sodium and potassium ion channels (HCN and KCNQ, the latter via the activation of protein kinase A [PKA]). The opening of ion channels results in depolarization of the neuron and, consequently, weakening of the network and impaired cognitive function. ATP adenosine triphosphate, Gi inhibitory G-protein