Elongation Factor 1A May Modulate Local Protein Synthesis At Hippocampal Dendritic Spines In The Mouse

Studies on the molecular mechanisms underlying long-term synaptic plasticity have been focused on the control of gene expression at the transcriptional level, but very little is known about the regulation of local translational events. We have recently shown that axonal translocation of the elongation factor 1A (EF1A), a translation factor that promotes the elongation of nascent polypeptide chains during protein synthesis, is associated with the late phase of long-term facilitation in Aplysia sensory-motor neuron synapses. To investigate whether EF1A may play a role in the regulation of synaptic plasticity in the mouse brain, we used confocal and electron microscopic immunocytochemistry with a monoclonal antibody (Upstate, NY). In perfused brains, we observed strong EF1A immunoreactivity (IR) in the soma of virtually every neuron in the brain. Furthermore, we detected moderate immunolabelling of dendritic profiles in different neuronal populations, including pyramidal cells of the hippocampus and cerebral cortex. Preembedding electron microscopy showed that EF1A immunolabelling of dendritic processes extended into post-synaptic specializations, whereas no IR was detected in presynaptic axonal terminals. We then studied the subcellular localization of EF1A in stratum radiatum of hippocampal slices following LTP induced by tetanic stimulation of Schaffer collaterals. Consistent with previous observations in the rat brain, LTP was associated with a rapid increase in the amount of EF1A-IR in the dendrites of CA1 pyramidal neurons. Furthermore, preliminary electron microscopic examination of stimulated slices showed that most of the dendritic spines in stratum radiatum were immunopositive for EF1A. Our results suggest that EF1A may be involved in coupling long-lasting synaptic activation with the regulation of local protein synthesis at individual dendritic spines.