Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activating Transcription Factor 2
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Active Transport, Cell Nucleus
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Adenylyl Cyclases / physiology*
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Animals
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Calcium / physiology*
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Calcium Signaling / physiology*
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Circadian Rhythm / physiology
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Cyclic AMP / physiology
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Cyclic AMP Response Element-Binding Protein / physiology
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Enzyme Activation
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Gene Expression Regulation, Developmental / genetics
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Gene Expression Regulation, Developmental / physiology
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Hippocampus / cytology
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Hippocampus / metabolism
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Humans
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Long-Term Potentiation / physiology*
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MAP Kinase Signaling System / physiology*
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Memory / physiology*
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Mice
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Mossy Fibers, Hippocampal / physiology
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Nerve Tissue Proteins / physiology*
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Neurons / physiology
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Receptors, N-Methyl-D-Aspartate / physiology
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Regulatory Sequences, Nucleic Acid
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Transcription Factors / physiology
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Transcription, Genetic
Substances
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Activating Transcription Factor 2
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Cyclic AMP Response Element-Binding Protein
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Nerve Tissue Proteins
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Receptors, N-Methyl-D-Aspartate
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Transcription Factors
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Cyclic AMP
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Adenylyl Cyclases
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Calcium