title: Increases in cAMP, MAPK activity, and CREB phosphorylation during REM sleep: implications for REM sleep and memory consolidation.
abstract: The cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and cAMP response element-binding protein (CREB) transcriptional pathway is required for consolidation of hippocampus-dependent memory. In mice, this pathway undergoes a circadian oscillation required for memory persistence that reaches a peak during the daytime. Because mice exhibit polyphasic sleep patterns during the day, this suggested the interesting possibility that cAMP, MAPK activity, and CREB phosphorylation may be elevated during sleep. Here, we report that cAMP, phospho-p44/42 MAPK, and phospho-CREB are higher in rapid eye movement (REM) sleep compared with awake mice but are not elevated in non-REM sleep. This peak of activity during REM sleep does not occur in mice lacking calmodulin-stimulated adenylyl cyclases, a mouse strain that learns but cannot consolidate hippocampus-dependent memory. We conclude that a preferential increase in cAMP, MAPK activity, and CREB phosphorylation during REM sleep may contribute to hippocampus-dependent memory consolidation.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195-7750, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Trongha X
authors.initials: TX
authors.lastname: Phan
authors.forename: Yimei
authors.initials: Y
authors.lastname: Yang
authors.forename: Michael G
authors.initials: MG
authors.lastname: Garelick
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000502:physiology; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology; D004569:Electroencephalography / Q000379:methods / Q000523:psychology; D004576:Electromyography / Q000379:methods / Q000523:psychology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D012895:Sleep, REM / Q000235:genetics / Q000502:physiology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; C118292:adenylyl cyclase 8