Consolidation of hippocampus dependent memory is dependent on activation of the cAMP/Erk/MAPK signal transduction pathway in the hippocampus. Recently, we discovered that adenylyl cyclase and MAPK activities undergo a circadian oscillation in the hippocampus and that inhibition of this oscillation pharmacologically or genetically impairs contextual memory. This suggests the interesting possibility that the persistence of hippocampus-dependent memory depends upon the reactivation of MAPK in the hippocampus during the circadian cycle. A key unanswered question is whether the circadian oscillation of this signaling pathway is intrinsic to the hippocampus or is driven by the master circadian clock in the suprachiasmatic nucleus (SCN). To address this question, we ablated the SCN of mice by electrolytic lesion and examined hippocampus-dependent memory as well as adenylyl cyclase and MAPK activities. Electrolytic lesion of the SCN two days after training for contextual fear memory reduced contextual memory measured two weeks after training indicating that maintenance of contextual memory depends on the SCN. Spatial memory was also compromised in SCN-lesioned mice. Furthermore, the circadian oscillation of adenylyl cyclase and MAPK activities in the hippocampus was destroyed by lesioning of the SCN. We also utilize arrhythmic model of animals, the Bmal1 KO, without the Bmal1, the animals display no locomotor rhythm activities. We also found that these mice have severe deficit in learning spatial memory task such as the Morris water maze, and contextual fear conditioning. Furthermore, the MAPK activities in these animals are nonoscillatory in the hippocampus. These data suggest that hippocampus-dependent long-term memory is dependent on the SCN-controlled oscillation of the adenylyl cyclase/MAPK pathway in the hippocampus.