Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortex
Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortex
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DOI：
10.1073/pnas.0609596104
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发表时间：
2007-01-23
影响因子：
11.1
通讯作者：
Bear, Mark F.
中科院分区：
文献类型：
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作者：
Crozier, Robert A.;Wang, Yun;Bear, Mark F.
低频突触刺激（LFS）诱导的长期抑制（LTD）最初是作为一种研究剥夺性突触抑制的潜在机制的模型而引入的。在海马中，LTD需要激活突触后NMDA受体、PKA和网格蛋白依赖的α -氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的内吞。长期以来，人们一直认为视觉皮层第4层的LFS在第2/3层诱导的LTD使用类似的机制。在这里，我们在小鼠视觉皮层中显示，这一结论需要修正。我们发现LFS在第2/3层诱导的LTD不受PKA抑制剂或α -氨基-3-羟基-5-甲基-4-异恶唑烯丙酸受体内吞噬的影响，但可靠地被内源性大麻素CB1受体拮抗剂阻断。相反，LFS应用于第4层神经元突触产生的LTD在机制上与CA1相同，并且对CB1阻滞剂不敏感。遮挡实验表明，这两种机制都有助于单眼剥夺后视觉反应性的丧失。
Long-term depression (LTD) induced by low-frequency synaptic stimulation (LFS) was originally introduced as a model to probe potential mechanisms of deprivation-induced synaptic depression in visual cortex. In hippocampus, LTD requires activation of,postsynaptic NMDA receptors, PKA, and the clathrin-dependent endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. It has long been assumed that LTD induced in visual cortical layer 2/3 by LFS of layer 4 uses similar mechanisms. Here we show in mouse visual cortex that this conclusion requires revision. We find that LTD induced in layer 2/3 by LFS is unaffected by inhibitors of PKA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor endocytosis but is reliably blocked by an endocannabinoid CB1 receptor antagonist. Conversely, LFS applied to synapses on layer 4 neurons produces LTD that appears mechanistically identical to that in CA1 and is insensitive to CB1 blockers. Occlusion experiments suggest that both mechanisms contribute to the loss of visual responsiveness after monocular deprivation.