Although the circadian time-keeping properties of the suprachiasmatic nucle
i (SCN) require gene expression, little is known about the signal transduct
ion pathways that initiate transcription. Here we report that a brief expos
ure to light during the subjective night, but not during the subjective day
, activates the p44/42 mitogen-activated protein kinase (MAPK) signaling ca
scade in the SCN. In addition, MAPK stimulation activates CREB (cAMP respon
se element binding protein), indicating that potential downstream transcrip
tion factors are stimulated by the MAPK pathway in the SCN. We also observe
d striking circadian variations in MAPK activity within the SCN, suggesting
that the MAPK cascade is involved in crock rhythmicity.