Functions and mechanisms of BDNF mRNA trafficking

Long-lasting changes in the basis of memory storage require delivery of newly synthesized proteins to the affected synapses. While most of these proteins are generated in the cell body, several key molecules for plasticity can be delivered in the form of silent mRNAs at synapses in extra-somatic compartments where they are locally translated in response to specific stimuli. One such mRNA encodes brain derived neurotrophic factor (BDNF), a key molecule in neuronal development that plays a critical role in learning and memory, and which displays abnormal levels in several neuropsychiatric disorders. BDNF mRNA accumulates in distal dendrites in response to stimuli that trigger activation of NMDAR and TrkB receptors. A single BDNF protein is produced from several splice variants having different 5'UTRs. We have shown that these mRNA variants have a different subcellular localization (soma, proximal or distal dendritic compartment) and that the protein is co-localized with the transcript from which it originated. As these splice variants are also differentially expressed in response to various stimuli and antidepressants, we propose that they represent a spatial and temporal code to regulate BDNF protein expression locally.