Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses
Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses
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DOI：
10.1093/emboj/20.21.5887
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发表时间：
2001-11-01
期刊：
影响因子：
11.4
通讯作者：
Lessmann, V
中科院分区：
文献类型：
--
作者：
Hartmann, M;Heumann, R;Lessmann, V
脑源性神经营养因子（BDNF）蛋白被认为是长期增强和其他形式的活动依赖性突触可塑性的逆行或旁分泌突触信使。尽管对这一概念至关重要，但缺乏BDNF活动依赖性突触释放的直接证据。本研究通过监测活海马神经元谷氨酸能突触连接处树突状BDNF- gfp囊泡的荧光强度变化，研究绿色荧光蛋白标记BDNF的分泌。我们发现谷氨酸能突触的高频激活触发了BDNF-GFP从突触局部分泌颗粒的释放。这种释放依赖于突触后嗜离子性谷氨酸受体的激活和突触后Ca2+内流。BDNF- gfp的释放也可以从突触外树突囊泡簇中观察到，这表明BDNF释放到特定突触位点的空间限制可能只发生在突触后去极化保持局部的情况下。这些结果支持BDNF是活动依赖性突触可塑性的突触信使的概念，它是从突触后神经元释放的。
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.