(A) Effect of HCN channel blocker ZD7288 (arrowhead) on SCN mPER2:LUC circadian gene expression. (B) Damping of peak bioluminescence in SCN slices treated with vehicle or ZD7288 (Pre= pre-treatment, Mean±SEM, n>4). (C) Brefeldin A suppresses circadian gene expression in PER2::LUC SCN. (D) Transient re-activation of MDL-suppressed circadian PER2::LUC expression in SCN slices by Sp-8-CPT-2′-O-Me-cAMPS. (E) Acute activation of cellular circadian gene expression (expressed as relative grey scale units) by Epac agonist in presence of MDL, illustrated by raster (upper panel) and graphical plots (lower panel) of 20 representative cells. (F) Phase shifts of SCN circadian PER2::LUC bioluminescence rhythm by Epac agonist (Sp-8-CPT-2′-O-Me-cAMP, red) but not vehicle (black, mean±SEM, n>3 per time point, ** p<0.01 vs. vehicle, ANOVA and Bonferroni).