Synaptic Activity Controls Dendritic Spine Morphology by Modulating eEF2-Dependent BDNF Synthesis

• DOI: 10.1523/jneurosci.0119-10.2010
• Publication Date: 2010-04-28T16:53:04Z
• Authors: Chiara Verpelli; Giovanni Piccoli; Cristina Zibetti; Alice Zanchi; Fabrizio Gardoni; Kun Huang; Dario Brambilla; Monica Di Luca; Elena Battaglioli; Carlo Sala
• Keywords: Elongation Factor 2 Kinase; Neurons; 0301 basic medicine; Brain-Derived Neurotrophic Factor; Dendritic Spines; In Vitro Techniques; Receptors, Metabotropic Glutamate; Hippocampus; Synaptic Transmission; Rats; 03 medical and health sciences; Peptide Elongation Factor 2; Gene Knockdown Techniques; Synapses; Animals; RNA Interference; Phosphorylation; Cells, Cultured; Signal Transduction

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, BDNF overexpression 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. We propose that the eEF2K/eEF2 pathway is a key biochemical sensor that couple neuronal activity to spine plasticity, by controlling the dendritic translation of BDNF.