Early presynaptic and late postsynaptic components contribute independently to brain-derived neurotrophic factor-induced synaptic plasticity
Early presynaptic and late postsynaptic components contribute independently to brain-derived neurotrophic factor-induced synaptic plasticity
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DOI：
10.1523/jneurosci.2970-04.2005
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发表时间：
2005-03-23
影响因子：
5.3
通讯作者：
Black, IB
中科院分区：
文献类型：
--
作者：
Alder, J;Thakker-Varia, S;Black, IB
肌蛋白诱导的突触可塑性由突触前和突触后过程组成。这些机制的潜在相互依赖性及其时间关系尚未定义。突触小泡蛋白 Rab3A 在 BDNF 增强传递的早期、初始 10 分钟阶段是必需的，但在后期则不需要。我们现在研究 BDNF 作用这些阶段之间的时间区别和机制关系。 Rab3A 突变细胞在细胞培养物中并未表现出响应 BDNF 的微型 EPSC 频率增加，表明不存在突触前成分。相反，与野生型一样，BDNF 增强突变神经元中谷氨酸诱导的突触后电流，表明反应的突触后成分是完整的。最后，在 Rab3A 敲除中，突触后 NMDA 受体亚基 NR2B 在 Tyr(1472) 处被 BDNF 磷酸化，如之前在野生型中所示。我们的结果首次证明 BDNF 增强的突触活动的突触前和突触后成分是独立的且在时间上是不同的。
Trophin-induced synaptic plasticity consists of both presynaptic and postsynaptic processes. The potential interdependence of these mechanisms and their temporal relationships are undefined. The synaptic vesicle protein Rab3A is required for the early, initial 10min phase but not for the later phase of BDNF-enhanced transmission. We now examine the temporal distinction and mechanistic relationships between these phases of BDNF action. Rab3A mutant cells did not exhibit increased miniature EPSC frequency in response to BDNF in cell culture, indicating an absence of the presynaptic component. In contrast, BDNF enhanced postsynaptic glutamate-induced current in the mutant neurons as in the wild type, indicating that the postsynaptic component of the response was intact. Finally, the postsynaptic NMDA receptor subunit NR2B was phosphorylated at Tyr(1472) by BDNF in Rab3A knock-outs, as shown previously in wild type. Our results are the first to demonstrate that presynaptic and postsynaptic components of BDNF-enhanced synaptic activity are independent and temporally distinct.