title: Signaling from cAMP/PKA to MAPK and synaptic plasticity.
abstract: The facilitation of hippocampus-based, long-lasting synaptic plasticity, which is frequently investigated in model systems such as long-term potentiation (LTP) and in learning paradigms such as the Morris water maze, is associated with several cellular key events: Ca(2+) influx through the N-methyl-D-aspartate (NMDA) receptor, generation of cyclic AMP (cAMP) and activation of protein kinase A (PKA), phosphorylation of mitogen-associated protein kinase (MAPK) and cAMP-response element-binding protein (CREB), and subsequent transcription of plasticity-associated genes. Recently, a signal-transduction cascade from cAMP/PKA to MAPK was discovered, which seems to be neuron-specific and comprises the critical events of hippocampus-based long-term plasticity described here into one single cascade. A major alternative to cAMP/PKA-MAPK signaling are the cascades from Ca(2+) to MAPK via Ras. However, Ras is inhibited by PKA. This article reviews the studies that argue for the existence of two competing pathways, and discusses their implication for the molecular mechanisms underlying synaptic plasticity.
authors.affiliation: Department of Neurology, University of Tübingen, Germany. robert.waltereit@uni-tuebingen.de
authors.forename: Robert
authors.initials: R
authors.lastname: Waltereit
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000201:enzymology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D018631:ras Proteins