Abstract
Restricted and regulated expression in mice of VP16-CREB, a constitutively active form of CREB, in hippocampal CA1 neurons lowers the threshold for eliciting a persistent late phase of long-term potentiation (L-LTP) in the Schaffer collateral pathway. This L-LTP has unusual properties in that its induction is not dependent on transcription. Pharmacological and two-pathway experiments suggest a model in which VP16-CREB activates the transcription of CRE-driven genes and leads to a cell-wide distribution of proteins that prime the synapses for subsequent synapse-specific capture of L-LTP by a weak stimulus. Our analysis indicates that synaptic capture of CRE-driven gene products may be sufficient for consolidation of LTP and provides insight into the molecular mechanisms of synaptic tagging and synapse-specific potentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Doxycycline / pharmacology
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Electrophysiology
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Excitatory Postsynaptic Potentials / physiology
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Genes, Reporter
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Hippocampus / cytology
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Hippocampus / metabolism
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In Situ Hybridization
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In Vitro Techniques
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Long-Term Potentiation / physiology*
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Memory / physiology
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Mice
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Mice, Transgenic
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Models, Biological
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Neuronal Plasticity / physiology*
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Neurons / cytology
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Neurons / metabolism*
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Protein Biosynthesis
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Receptors, N-Methyl-D-Aspartate / metabolism
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Recombinant Fusion Proteins / metabolism
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Synapses / metabolism*
Substances
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Cyclic AMP Response Element-Binding Protein
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Receptors, N-Methyl-D-Aspartate
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Recombinant Fusion Proteins
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Cyclic AMP-Dependent Protein Kinases
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Doxycycline