Abstract
Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has been implicated in the regulation of CRE-dependent transcription. To investigate the role of this kinase in neuronal plasticity and memory, we generated transgenic mice in which the expression of a dominant-negative form of CaMKIV (dnCaMKIV) is restricted to the postnatal forebrain. In these transgenic mice, activity-induced CREB phosphorylation and c-Fos expression were significantly attenuated. Hippocampal late LTP (L-LTP) was also impaired, whereas basic synaptic function and early LTP (E-LTP) were unaffected. These deficits correlated with impairments in long-term memory, specifically in its consolidation/retention phase but not in the acquisition phase. These results indicate that neural activity-dependent CaMKIV signaling in the neuronal nucleus plays an important role in the consolidation/retention of hippocampus-dependent long-term memory.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Substitution
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Animals
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Brain / physiology*
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COS Cells
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases / chemistry
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Calcium-Calmodulin-Dependent Protein Kinases / genetics*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Chlorocebus aethiops
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Cyclic AMP Response Element-Binding Protein / metabolism
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Electric Stimulation
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Excitatory Postsynaptic Potentials / physiology
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Hippocampus / physiology
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In Situ Hybridization
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In Vitro Techniques
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Luciferases / genetics
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Maze Learning / physiology*
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Memory / physiology*
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Mice
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Mice, Transgenic
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Mutagenesis, Site-Directed
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Neuronal Plasticity
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Neurons / physiology*
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Prosencephalon / physiology
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Signal Transduction / physiology*
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Transfection
Substances
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Cyclic AMP Response Element-Binding Protein
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Recombinant Proteins
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Luciferases
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases
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Camk4 protein, mouse