Involvement of calcium-calmodulin protein kinase but not mitogen-activatedprotein kinase in light-induced phase delays and Per gene expression in the suprachiasmatic nucleus of the hamster

It is known that Ca2+-dependent phosphorylation of cAMP response element bi nding protein (CREB) and the rapid induction of mPer1 and mPer2, mouse peri od genes in the suprachiasmatic nucleus (SCN) are associated with light-ind uced phase shifting. The CREB/CRE transcriptional pathway has been shown to be activated by calcium/calmodulin dependent kinase II (CaMKII) and mitoge n-activated protein kinase (MAPK); however, there is a lack of evidence con cerning whether the activation of CaMKII and/or MAPK elicited by photic sti muli are associated with the change in Per gene expression and behavioral p hase shifting. In this experiment, we found there was an inhibitory effect by KN93, CaMKII inhibitor, on hamster Per1 and Per2 expression in the SCN a nd on phase delays in wheel running rhythm induced by light pulses. PD98059 and U0126, MAPK kinase inhibitors, however, affected neither light-induced Per1 and Per2 expression nor behavioral phase delays, even though PD98059 attenuated the light-induced phosphorylation of MAPK in the SCN. The presen t findings demonstrate that the light-induced activation of CaMKII plays an important role in the induction of Per1 and Per2 mRNA in the hamster SCN a s well as phase shifting. These results suggest that gated induction of Per 1 and/or Per2 genes through CaMKII-CREB/CRE accompanied with photic stimuli may be a critical step in phase shifting.