Disruption of Dendritic Translation of CaMKIIα Impairs Stabilization of Synaptic Plasticity and Memory Consolidation
Copyright policy )Disruption of Dendritic Translation of CaMKIIα Impairs Stabilization of Synaptic Plasticity and Memory Consolidation
Local protein translation in dendrites could be a means for delivering synaptic proteins to their sites of action, perhaps in a spatially regulated fashion that could contribute to plasticity. To directly test the functional role of dendritic translation of calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) in vivo, we mutated the endogenous gene to disrupt the dendritic localization signal in the mRNA. In this mutant mouse, the protein-coding region of CaMKIIalpha is intact, but mRNA is restricted to the soma. Removal of dendritic mRNA produced a dramatic reduction of CaMKIIalpha in postsynaptic densities (PSDs), a reduction in late-phase long-term potentiation (LTP), and impairments in spatial memory, associative fear conditioning, and object recognition memory. These results demonstrate that local translation is important for synaptic delivery of the kinase and that local translation contributes to synaptic and behavioral plasticity.
- University of California, San Diego United States
- Scripps Research Institute United States
- Department of Neuroscience Italy
- University of California, San Diego United States
Memory Disorders, Behavior, Animal, Chimera, Neuroscience(all), Long-Term Potentiation, Mice, Transgenic, Dendrites, Fear, Hippocampus, Gene Expression Regulation, Enzymologic, Mice, Organ Culture Techniques, Phenotype, Memory, Calcium-Calmodulin-Dependent Protein Kinases, Gene Targeting, Mutation, Animals, Protein Isoforms, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Maze Learning
Memory Disorders, Behavior, Animal, Chimera, Neuroscience(all), Long-Term Potentiation, Mice, Transgenic, Dendrites, Fear, Hippocampus, Gene Expression Regulation, Enzymologic, Mice, Organ Culture Techniques, Phenotype, Memory, Calcium-Calmodulin-Dependent Protein Kinases, Gene Targeting, Mutation, Animals, Protein Isoforms, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Maze Learning
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