Down-regulation of drebrin A expression suppresses synaptic targeting of NMDA receptors in developing hippocampal neurones.

Drebrin is a major F-actin-binding protein in the brain. We have recently demonstrated that drebrin A (neurone-specific isoform) clusters at synapses and governs targeting of the post-synaptic density 95 protein to synapses during development. To determine the role of drebrin A on excitatory synapse formation, we analysed whether the suppression of drebrin A expression affects filopodia-spine morphology and synaptic targeting of NMDA receptors in cultured hippocampal neurones. Suppression of developmentally programmed up-regulation of drebrin A by antisense treatment significantly decreased the density and width of filopodia-spines. Immunocytochemistry showed that the antisense treatment did not attenuate synaptic clustering of NMDA receptors under conditions that permitted spontaneous activities but inhibited the accelerated targeting of NMDA receptors into synapses by its antagonist D-(-)-2-amino-5-phosphonopentanoic acid. These results indicate that drebrin A up-regulation plays a pivotal role in spine morphogenesis and activity-dependent synaptic targeting of NMDA receptors.