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 IIα (CaMKIIα) 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 CaMKIIα is intact, but mRNA is restricted to the soma. Removal of dendritic mRNA produced a dramatic reduction of CaMKIIα 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.
