Fig. 6.

Working model of β1-AR mechanisms in layer III dlPFC

We hypothesize that high levels of NE release during stress engage low affinity β1-ARs, which take dlPFC “offline” to switch control of behavior to more primitive circuits, e.g. mediated by the amygdala. The data indicate that β1-AR can reduce the firing of dlPFC Delay cells by at least two mechanisms: (A) The current study shows that β1-AR are expressed on GABAergic interneurons, including PV-expressing interneurons, where β1-AR drive GABAergic inhibition of pyramidal cell firing. (B) Our previous work has shown that β1-ARs are also highly concentrated on the dendritic spines of pyramidal cells, that weaken recurrent excitation by increasing cAMP-calcium opening of nearby K⁺ channels, reducing the recurrent excitatory connections needed for working memory. As interneurons are activated by pyramidal cells as well as by β1-AR, the loss of pyramidal cell firing would ultimately reduce PV interneuron firing as well, where the entire microcircuit may have low levels of firing. Note that the roles of calretinin (CR)- and calbindin (CB)-expressing interneurons are still to be determined, but β1-AR excitation of CB-expressing interneurons would theoretically add to pyramidal cell inhibition.