Local presynaptic activity gates homeostatic changes in presynaptic function driven by dendritic BDNF synthesis.
Local presynaptic activity gates homeostatic changes in presynaptic function driven by dendritic BDNF synthesis.
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DOI：
10.1016/j.neuron.2010.11.034
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发表时间：
2010-12-22
期刊：
影响因子：
16.2
通讯作者：
Sutton, Michael A.
中科院分区：
文献类型：
--
作者：
Jakawich, Sonya K.;Nasser, Hassan B.;Strong, Michael J.;McCartney, Amber J.;Perez, Amanda S.;Rakesh, Neal;Carruthers, Cynthia J. L.;Sutton, Michael A.
稳态突触可塑性对于维持神经元功能的稳定性是重要的，但异质性表达机制表明，神经元活动的不同方面可能会形成补偿性突触变化的方式。在这里，我们证明了本地突触前活动门的逆行形式的稳态可塑性诱导的AMPA受体（AMPAR）在培养的海马神经元阻断。我们发现，AMPAR阻断产生快速（< 3小时）的突触前和突触后功能的蛋白质合成依赖性增加，突触前，而不是突触后，变化的诱导需要在突触前末梢的一致的局部活动。这种突触前功能的“状态依赖性”调节需要突触后释放脑源性神经营养因子（BDNF）作为逆行信使，其响应于AMPAR阻断而在树突中局部合成。两者合计，我们的研究结果揭示了活跃的突触前末梢和突触后信号传导之间的局部串扰，该信号传导决定了在突触处实现稳态可塑性的方式。
Homeostatic synaptic plasticity is important for maintaining stability of neuronal function, but heterogeneous expression mechanisms suggest that distinct facets of neuronal activity may shape the manner in which compensatory synaptic changes are implemented. Here, we demonstrate that local presynaptic activity gates a retrograde form of homeostatic plasticity induced by blockade of AMPA receptors (AMPARs) in cultured hippocampal neurons. We show that AMPAR blockade produces rapid (< 3 hrs) protein synthesis-dependent increases in both presynaptic and postsynaptic function, and that the induction of presynaptic, but not postsynaptic, changes requires coincident local activity in presynaptic terminals. This “state-dependent” modulation of presynaptic function requires postsynaptic release of brain-derived neurotrophic factor (BDNF) as a retrograde messenger, which is locally synthesized in dendrites in response to AMPAR blockade. Taken together, our results reveal a local cross-talk between active presynaptic terminals and postsynaptic signaling that dictates the manner by which homeostatic plasticity is implemented at synapses.
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