title: The diurnal oscillation of MAP (mitogen-activated protein) kinase and adenylyl cyclase activities in the hippocampus depends on the suprachiasmatic nucleus.
abstract: Consolidation of hippocampus-dependent memory is dependent on activation of the cAMP/Erk/MAPK (mitogen-activated protein kinase) 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 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 2 d after training for contextual fear memory reduced contextual memory measured 2 weeks after training, indicating that maintenance of contextual memory depends on the SCN. Spatial memory was also compromised in SCN-lesioned mice. Furthermore, the diurnal oscillation of adenylyl cyclase and MAPK activities in the hippocampus was destroyed by lesioning of the SCN. 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.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195-7750, USA.
authors.forename: Trongha X
authors.initials: TX
authors.lastname: Phan
authors.forename: Trongha H
authors.initials: TH
authors.lastname: Phan
authors.forename: Guy C-K
authors.initials: GC
authors.lastname: Chan
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Sindreu
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Eckel-Mahan
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004572:Electrolysis / Q000379:methods; D005106:Exploratory Behavior; D006624:Hippocampus / Q000201:enzymology*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009434:Neural Pathways / Q000502:physiology; D021641:Recognition, Psychology; D013028:Space Perception / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000293:injuries / Q000502:physiology*; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
chemical_list: D014316:Tritium; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; D000262:Adenylyl Cyclases; D002118:Calcium