Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation

Stephan Miller; Masahiro Yasuda; Jennifer K Coats; Ying Jones; Maryann E Martone; Mark Mayford

doi:10.1016/s0896-6273(02)00978-9

Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation

Neuron. 2002 Oct 24;36(3):507-19. doi: 10.1016/s0896-6273(02)00978-9.

Authors

Stephan Miller¹, Masahiro Yasuda, Jennifer K Coats, Ying Jones, Maryann E Martone, Mark Mayford

Affiliation

¹ Department of Cell Biology and Institute for Childhood and Neglected Diseases, The Scripps Research Institute, 10550 North Torrey Pines Road, ICND 202, La Jolla, CA 92037, USA. stephanm@scripps.edu

PMID: 12408852
DOI: 10.1016/s0896-6273(02)00978-9

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Behavior, Animal / physiology
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases / deficiency*
Calcium-Calmodulin-Dependent Protein Kinases / genetics
Chimera
Dendrites / enzymology*
Fear / physiology
Gene Expression Regulation, Enzymologic / genetics
Gene Targeting
Hippocampus / cytology
Hippocampus / enzymology*
Hippocampus / growth & development*
Long-Term Potentiation / genetics*
Maze Learning / physiology
Memory / physiology*
Memory Disorders / enzymology
Memory Disorders / genetics
Memory Disorders / physiopathology
Mice
Mice, Transgenic
Mutation / genetics
Organ Culture Techniques
Phenotype
Protein Isoforms / deficiency
Protein Isoforms / genetics
Synaptic Membranes / genetics
Synaptic Membranes / metabolism
Synaptic Transmission / genetics*

Substances

Protein Isoforms
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Camk2a protein, mouse