Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses

The protein brain-derived neurotrophic factor (BDNF) has been postulated to be a retrograde or paracrine synaptic messenger in long-term potentiation and other forms of activity-dependent synaptic plasticity. Although crucial for this concept, direct evidence for the activity-dependent synaptic rele ase of BDNF is lacking. Here we investigate secretion of BDNF labelled with green fluorescent protein (BDNF-GFP) by monitoring the changes in fluoresc ence intensity of dendritic BDNF-GFP vesicles at glutamatergic synaptic jun ctions of living hippocampal neurons. We show that high-frequency activatio n of glutamatergic synapses triggers the release of BDNF-GFP from synaptica lly localized secretory granules. This release depends on activation of pos tsynaptic ionotropic glutamate receptors and on postsynaptic Ca2+ influx. R elease of BDNF-GFP is also observed from extrasynaptic dendritic vesicle cl usters, suggesting that a possible spatial restriction of BDNF release to s pecific synaptic sites can only occur if the postsynaptic depolarization re mains local. These results support the concept of BDNF being a synaptic mes senger of activity-dependent synaptic plasticity, which is released from po stsynaptic neurons.