Distinct subsets of Syt-IV/BDNF vesicles are sorted to axons versus dendrites and recruited to synapses by activity.
Distinct subsets of Syt-IV/BDNF vesicles are sorted to axons versus dendrites and recruited to synapses by activity.
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DOI：
10.1523/jneurosci.4515-11.2012
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发表时间：
2012-04-18
期刊：
影响因子：
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通讯作者：
Chapman ER
中科院分区：
文献类型：
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作者：
Dean C;Liu H;Staudt T;Stahlberg MA;Vingill S;Bückers J;Kamin D;Engelhardt J;Jackson MB;Hell SW;Chapman ER
BDNF在突触强度的调节中起着关键作用，并且对于长时程增强（LTP）是必不可少的，LTP是学习和记忆的基础现象。然而，BDNF是否以扩散的方式起作用，或者靶向特定的神经元亚区室或突触部位以影响回路功能，仍然是未知的。在这里，使用BDNF或syt-IV（一种调节含BDNF囊泡的胞吐作用的调节剂）在转染的大鼠海马神经元中的光活化，我们发现BDNF囊泡的不同子集被靶向轴突与树突，并且在这些隔室之间不共享。此外，syt-IV和BDNF-窝藏囊泡募集到突触前和突触后的网站，以响应增加的神经元活动。最后，使用syt-IV敲除小鼠神经元，我们发现，syt-IV是必要的突触前和突触后缩放的突触强度在网络活动的变化。这些发现表明，含有BDNF的囊泡可以靶向神经元中的特定位点，并表明syt-IV调节的BDNF分泌受到空间控制，以位点特异性方式调节突触功能。
BDNF plays a critical role in the regulation of synaptic strength and is essential for long-term potentiation (LTP), a phenomenon that underlies learning and memory. However, whether BDNF acts in a diffuse manner, or is targeted to specific neuronal sub-compartments or synaptic sites to affect circuit function, remains unknown. Here, using photoactivation of BDNF or syt-IV (a regulator of exocytosis present on BDNF-containing vesicles) in transfected rat hippocampal neurons, we discovered that distinct subsets of BDNF vesicles are targeted to axons versus dendrites and are not shared between these compartments. Moreover, syt-IV and BDNF-harboring vesicles are recruited to both pre and post-synaptic sites in response to increased neuronal activity. Finally, using syt-IV knockout mouse neurons, we found that syt-IV is necessary for both pre- and post-synaptic scaling of synaptic strength in response to changes in network activity. These findings demonstrate that BDNF-containing vesicles can be targeted to specific sites in neurons, and suggest that syt-IV-regulated BDNF secretion is subject to spatial control to regulate synaptic function in a site-specific manner.