KN-62, AN INHIBITOR OF CA2+ CALMODULIN KINASE-II, ATTENUATES CIRCADIAN RESPONSES TO LIGHT/

EXPRESSION of immediate early genes and phosphorylation of the transcr iption factor CREB are induced in the suprachiasmatic nucleus after li ght pulses that cause phase shifts of circadian rhythms. To test for a direct role of this signalling pathway in mediating circadian respons es to light in hamsters, we used KN-62 to inhibit the activity of CaM kinase II (known to phosphorylate CREB) prior to giving light pulses a t times that would normally induce phase shifts. Central administratio n of KN-62 significantly inhibited phase delays and advances induced b y bright pulses of light. The data support a model for photic response s of the circadian clock in the SCN that includes the phosphorylation of CREB by activation of CaM kinase II.