Involvement of calcium-calmodulin protein kinase but not mitogen-activated protein 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 binding protein (CREB) and the rapid induction of mPer1 and mPer2, mouse period genes in the suprachiasmatic nucleus (SCN) are associated with light-induced phase shifting. The CREB/CRE transcriptional pathway has been shown to be activated by calcium/calmodulin dependent kinase II (CaMKII) and mitogen-activated protein kinase (MAPK); however, there is a lack of evidence concerning whether the activation of CaMKII and/or MAPK elicited by photic stimuli are associated with the change in Per gene expression and behavioral phase shifting. In this experiment, we found there was an inhibitory effect by KN93, CaMKII inhibitor, on hamster Per1 and Per2 expression in the SCN and 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 present 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 as well as phase shifting. These results suggest that gated induction of Per1 and/or Per2 genes through CaMKII-CREB/CRE accompanied with photic stimuli may be a critical step in phase shifting.