Role of Ca2+-stimulated adenylyl cyclases in LTP and memory formation.
Studies with invertebrates and vertebrates have strongly implicated the CREB/CRE transcriptional pathway in long-term memory (LTM) and transcriptionally-dependent L-LTP. It is hypothesized that LTM and L-LTP are both dependent upon a Ca2+ signal generated through activation of NMDA receptors. This review discusses evidence that Ca2+ signals generated through activation of NMDA receptors coactivate the Erk/MAP kinase and cAMP signal transduction pathways. It is hypothesized that activation of these two regulatory pathways increases the transcription of a family of genes through the CREB/CRE transcriptional pathway. Gene disruption studies have shown that Ca2+ activated adenylyl cyclases play a critical role in generating the cAMP signal required for LTM and L-LTP. Although cAMP may be required for several events in this complex signal transduction cascade, one of the major roles of cAMP may be to support nuclear translocation of Erk/MAP kinase in hippocampal neurons.
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Department of Pharmacology, University of Washington, Health Sciences Building, Mail Box 357750, Seattle, WA 98195-7750, USA.
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D051698:Activating Transcription Factor 2; D021581:Active Transport, Cell Nucleus; D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium