Decrease in calcium concentration triggers neuronal retinoic acid synthesis during homeostatic synaptic plasticity.
Decrease in calcium concentration triggers neuronal retinoic acid synthesis during homeostatic synaptic plasticity.
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钙浓度的降低会在稳态突触可塑性期间触发神经元视黄酸合成
DOI：
10.1523/jneurosci.3964-11.2011
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发表时间：
2011-12-07
期刊：
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
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作者：
Wang HL;Zhang Z;Hintze M;Chen L
突触活性的阻断诱导稳态可塑性，部分是通过刺激全反式维甲酸（RA）的合成，从而增加AMPA受体的合成。然而，触发RA合成的突触信号仍然未知。使用多种活性阻断方案诱导稳态突触可塑性，这里我们表明，RA合成被激活时，突触后Ca2+进入显著减少，RA是必需的突触强度上调在这些稳态可塑性条件下，这表明Ca2+在RA合成中起抑制作用。与这一概念一致，我们证明了膜渗透性Ca2+螯合剂的瞬态Ca2+消耗和l型Ca2+通道的慢性阻塞都会诱导RA合成。此外，调节RA合成的树突Ca2+进入的来源并不特定，因为轻度的KCl去极化足以逆转l型Ca2+通道阻滞剂诱导的突触收缩。通过表达二氢吡啶不敏感的l型Ca2+通道，我们进一步表明RA细胞自主调节突触传递。我们的研究结果表明，在突触活跃的神经元中，适度的“基础”水平的突触后Ca2+在生理上抑制RA的合成，而在突触不活跃的神经元中，静息Ca2+水平的降低通过刺激RA的合成诱导稳态可塑性，然后以细胞自主的方式增加AMPA受体的功能。
Blockade of synaptic activity induces homeostatic plasticity, in part by stimulating synthesis of all-trans retinoic acid (RA), which in turn increases AMPA receptor synthesis. However, the synaptic signal that triggers RA synthesis remained unknown. Using multiple activity-blockade protocols that induce homeostatic synaptic plasticity, here we show that RA synthesis is activated whenever postsynaptic Ca2+ entry is significantly decreased and that RA is required for upregulation of synaptic strength under these homeostatic plasticity conditions, suggesting that Ca2+ plays an inhibitory role in RA synthesis. Consistent with this notion, we demonstrate that both transient Ca2+ depletion by membrane-permeable Ca2+ chelators and chronic blockage of L-type Ca2+-channels induces RA synthesis. Moreover, the source of dendritic Ca2+ entry that regulates RA synthesis is not specific because mild depolarization with KCl is sufficient to reverse synaptic scaling induced by L-type Ca2+-channel blocker. By expression of a dihydropyridine-insensitive L-type Ca2+ channel, we further show that RA acts cell autonomously to modulate synaptic transmission. Our findings suggest that, in synaptically active neurons, modest “basal” levels of postsynaptic Ca2+ physiologically suppress RA synthesis, whereas in synaptically inactive neurons, decreases in the resting Ca2+ levels induce homeostatic plasticity by stimulating synthesis of RA that then acts in a cell-autonomous manner to increase AMPA receptor function.