PMID- 11689429 OWN - NLM STAT- MEDLINE DCOM- 20011207 LR - 20220309 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 20 IP - 21 DP - 2001 Nov 1 TI - Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses. PG - 5887-97 AB - 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. FAU - Hartmann, M AU - Hartmann M AD - Department of Molecular Neurobiochemistry, Ruhr University Bochum, NC7-132, D-44780 Bochum, Germany. FAU - Heumann, R AU - Heumann R FAU - Lessmann, V AU - Lessmann V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Luminescent Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 3KX376GY7L (Glutamic Acid) RN - RWP5GA015D (Potassium) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/biosynthesis/genetics/*metabolism MH - Cells, Cultured MH - Dendrites/metabolism/ultrastructure MH - Electric Stimulation/methods MH - Glutamic Acid/*metabolism MH - Green Fluorescent Proteins MH - Hippocampus/cytology/metabolism MH - Luminescent Proteins/genetics MH - Membrane Potentials/drug effects MH - Microscopy, Video MH - Neurons/cytology/metabolism MH - Potassium/metabolism/pharmacology MH - Rats MH - Recombinant Fusion Proteins/biosynthesis/genetics/metabolism MH - Secretory Vesicles/metabolism MH - Synapses/*metabolism MH - Synaptic Vesicles/metabolism MH - Transfection PMC - PMC125691 EDAT- 2001/11/02 10:00 MHDA- 2002/01/05 10:01 PMCR- 2002/11/01 CRDT- 2001/11/02 10:00 PHST- 2001/11/02 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/11/02 10:00 [entrez] PHST- 2002/11/01 00:00 [pmc-release] AID - cde578 [pii] AID - 10.1093/emboj/20.21.5887 [doi] PST - ppublish SO - EMBO J. 2001 Nov 1;20(21):5887-97. doi: 10.1093/emboj/20.21.5887.