Abstract
The calcium-calmodulin-dependent kinase II (CaMKII) is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, CaMKII can undergo autophosphorylation, resulting in CaM-independent activity. A point mutation was introduced into the alphaCaMKII gene that blocked the autophosphorylation of threonine at position 286 (Thr286) of this kinase without affecting its CaM-dependent activity. The mutant mice had no N-methyl-D-aspartate receptor-dependent LTP in the hippocampal CA1 area and showed no spatial learning in the Morris water maze. Thus, the autophosphorylation of alphaCaMKII at Thr286 appears to be required for LTP and learning.
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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2-Amino-5-phosphonovalerate / pharmacology
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Animals
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Calmodulin / metabolism
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Gene Targeting
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Hippocampus / metabolism
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Hippocampus / physiology*
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Long-Term Potentiation* / drug effects
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Maze Learning*
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Patch-Clamp Techniques
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Phosphorylation
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Phosphothreonine / metabolism
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Picrotoxin / pharmacology
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Point Mutation
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Pyramidal Cells / physiology*
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Receptors, N-Methyl-D-Aspartate / physiology
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Synaptic Transmission
Substances
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Calmodulin
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Receptors, N-Methyl-D-Aspartate
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Phosphothreonine
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Picrotoxin
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-Amino-5-phosphonovalerate
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases