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 release of BDNF is lacking. Here we investigate secretion of BDNF labelled with green fluorescent protein (BDNF-GFP) by monitoring the changes in fluorescence intensity of dendritic BDNF-GFP vesicles at glutamatergic synaptic junctions of living hippocampal neurons. We show that high-frequency activation of glutamatergic synapses triggers the release of BDNF-GFP from synaptically localized secretory granules. This release depends on activation of postsynaptic ionotropic glutamate receptors and on postsynaptic Ca(2+) influx. Release of BDNF-GFP is also observed from extrasynaptic dendritic vesicle clusters, suggesting that a possible spatial restriction of BDNF release to specific synaptic sites can only occur if the postsynaptic depolarization remains local. These results support the concept of BDNF being a synaptic messenger of activity-dependent synaptic plasticity, which is released from postsynaptic neurons.
Hartmann
M
M
Department of Molecular Neurobiochemistry, Ruhr University Bochum, NC7-132, D-44780 Bochum, Germany.
Heumann
R
R
Lessmann
V
V
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004558:Electric Stimulation / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects; D018715:Microscopy, Video; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D011188:Potassium