Abstract
The Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca(2+) signaling; its function was analyzed by targeted gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP-responsive element binding protein (CREB) phosphorylation and Ca(2+)/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late phase of long-term depression in cerebellar Purkinje neurons. However, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits in spatial learning and memory. These results support an important role for CaMKIV/Gr in Ca(2+)-regulated neuronal gene transcription and synaptic plasticity and suggest that the contribution of other signaling pathways may spare spatial memory of CaMKIV/Gr-deficient mice.
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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Animals
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Brain / physiology
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Calcium Signaling / physiology
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases / deficiency
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cerebral Cortex / physiology*
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Electric Stimulation
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Hippocampus / physiology*
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Long-Term Potentiation
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Male
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Maze Learning / physiology*
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Memory
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Mice
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Mice, Knockout
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Motor Activity / physiology*
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Neuronal Plasticity / physiology*
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Neurons / physiology*
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Posture
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Purkinje Cells / physiology
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Pyramidal Cells / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Swimming
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Synapses / physiology*
Substances
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Cyclic AMP Response Element-Binding Protein
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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