Synaptic activity controls dendritic spine morphology by modulating eEF2-dependent BDNF synthesis.

Activity-dependent changes in synaptic structure and spine morphology are required for learning and memory, and depend on protein
translation. We show that the kinase for eukaryotic elongation factor 2 (eEF2K) regulates dendritic spine stability and synaptic structure
by modulating activity-dependent dendritic BDNF synthesis. Specifically RNAi knockdown of eEF2K reduces dendritic spine stability
and inhibits dendritic BDNF protein expression; whereas overexpression of a constitutively activated eEF2K induces spine maturation
and increases expression of dendritic BDNF. Furthermore,BDNFoverexpression rescues the spine stability reduced by RNAi knockdown
of eEF2K. We also show that synaptic activity-dependent spine maturation and dendritic BDNF protein expression depend on mGluR/
EF2K-induced eEF2 phosphorylation.Wepropose that the eEF2K/eEF2 pathway is a key biochemical sensor that couple neuronal activity
to spine plasticity, by controlling the dendritic translation of BDNF.