Studies on the activity-dependent translational control in neurons

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Activity-dependent local translation at the perisynaptic area is implicated in synapse-wide alterations of function and morphology. The molecular mechanisms of local translation activation, however, have yet to be illuminated. We have shown that local protein synthesis and translational activation in neuronal dendrites were up-regulated by brain-derived neurotrophic factor (BDNF) in a rapamycin-sensitive manner. In parallel, BDNF activates of mammalian target of rapamycin (mTOR) signaling pathways in dendrites. BDNF also enhances elongation process through the mTOR pathway. Inhibition of mTOR activity by rapamycin and knockdown of mTOR by siRNA completely suppresses the action of BDNF.The present results indicate that mTOR-dependent translation activation at multiple processes is essential for the up-regulation of local protein synthesis in neuronal dendrites. We further showed the evidences that mTOR-dependent translational activation occurred during plastic event, such as LTP and spatial memory paradigms in the CNS. As rapamycin canceled these effects, mTOR-dependent translational activation is essential for the certain types of neural plasticity.