Chemical-LTP induces confinment of BDNF mRNA under dendritic spines followed by BDNF protein accumulation inside the spines

Abstract

The neurotrophin brain-derived neurotrophic factor (BDNF) plays a key role in neuronal development and synaptic plasticity. The discovery that BDNF mRNA can be transported in neuronal dendrites in an activity-dependent manner has suggested that its local translation may support synapse maturation and plasticity. However, a clear demonstration that BDNF mRNA is locally transported and translated at activated synapses in response to long-term potentiation (LTP) is still lacking. Here, we study the dynamics of BDNF mRNA dendritic trafficking following induction of chemical-LTP (cLTP). Dendritic transport of BDNF transcripts was analysed using the MS2 system for mRNA visualization, and chimeric BDNF-GFP constructs were used to monitor protein synthesis in living neurons. We found that within 15 following cLTP induction, most BDNF mRNA granules become stationary and transiently accumulate in the dendritic shaft at the basis of the spines similarly to the control CamkII mRNA which increased also inside the spines, at 60 post-cLTP. At 60 but not at 15 from cLTP induction, we observed an increase in BDNF protein levels within the spine. Taken together, these findings suggest that BDNF mRNA trafficking is arrested in the early phase of cLTP, providing a local source of mRNA for translation of BDNF at the basis of the spine followed in the late LTP phase, by translocation of the BDNF protein within the spine head. StatementBrain-derived neurotrophic factor (BDNF) plays a key role in neuronal development and synaptic plasticity. In this study, we investigate two unresolved questions in neuronal plasticity: a) whether the post-synaptically released BDNF can be locally synthesized in this compartment, and b) whether the local translation of BDNF occurs in dendrites, or within the spine. Using chimeric constructs ectopically expressed in living primary hippocampal neurons, we tracked BDNF mRNA trafficking within the dendrites and its local translation following induction of chemical-LTP (cLTP) by forskolin. We show that in the early phase of cLTP induction (15), BDNF mRNA becomes confined at the basis of the spines providing a local source for translation of the protein followed in the late LTP phase (60), by translocation of the BDNF protein within the spine head.