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

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 Ca2+ 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

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

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Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
DOI
10.1093/emboj/20.21.5887
pmid
11689429
Publisher site
See Article on Publisher Site

Abstract

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 Ca2+ 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.

Journal

The EMBO JournalWiley

Published: Jan 1, 2001

Keywords: ; ; ; ;

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