The role of nitric oxide and GluR1 in presynaptic and postsynaptic components of neocortical potentiation
The role of nitric oxide and GluR1 in presynaptic and postsynaptic components of neocortical potentiation
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DOI：
10.1523/jneurosci.0652-06.2006
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发表时间：
2006-07-12
影响因子：
5.3
通讯作者：
Fox, Kevin
中科院分区：
文献类型：
--
作者：
Hardingham, Neil;Fox, Kevin
在这项研究中，我们研究了6-13周龄小鼠桶皮层IV层到II/III层通路的突触可塑性机制。这条通路是桶形皮层中经验依赖性可塑性表达的可能候选者之一，并可作为新皮层中其他IV至II/III突触的模型。我们发现，突触后autocamtide-2-抑制肽足以阻断长时程增强（LTP）（IC 50为500 nM），暗示突触后钙/钙调素依赖性激酶II在LTP诱导。AMPA受体亚基1（GluR 1）基因敲除小鼠也表现出LTP在这一途径中，但增强主要是突触前的起源所确定的成对脉冲分析，变异系数分析，和量子分析，而野生型表现出混合的突触前和突触后位点。通过测量锶存在下的单量子事件，验证了该突触的量子分析。GluR 1基因敲除的主要突触前LTP被一氧化氮合酶（NOS）的突触后拮抗作用阻断，无论是用细胞内N-ω-硝基-（L）-精氨酸甲酯还是N-硝基-（L）-精氨酸，为NO在该突触的逆行递质作用提供了第一个证据。野生型中NOS的拮抗作用显著降低，但没有消除LTP（组平均降低50%）。残留的LTP在每个细胞中形成了总LTP的可变比例，并被发现是突触后起源。我们在这个年龄段没有发现沉默突触的证据。最后，应用NO通过捐助者诱导增强层II/III细胞，并引起频率的增加，但不是幅度的微型EPSP，再次牵连NO突触前可塑性。
In this study, we investigated the mechanisms underlying synaptic plasticity at the layer IV to II/III pathway in barrel cortex of mice aged 6-13 weeks. This pathway is one of the likely candidates for expression of experience-dependent plasticity in the barrel cortex and may serve as a model for other IV to II/III synapses in the neocortex. We found that postsynaptic autocamtide-2-inhibitory peptide is sufficient to block long-term potentiation (LTP) (IC50 of 500 nM), implicating postsynaptic calcium/calmodulin-dependent kinase II in LTP induction. AMPA receptor subunit 1 (GluR1) knock-out mice also showed LTP in this pathway, but potentiation was predominantly presynaptic in origin as determined by paired-pulse analysis, coefficient of variation analysis, and quantal analysis, whereas wild types showed a mixed presynaptic and postsynaptic locus. Quantal analysis at this synapse was validated by measuring uniquantal events in the presence of strontium. The predominantly presynaptic LTP in the GluR1 knock-outs was blocked by postsynaptic antagonism of nitric oxide synthase (NOS), either with intracellular N-omega-nitro-(L)-arginine methyl ester or N-nitro-(L)-arginine, providing the first evidence for a retrograde transmitter role for NO at this synapse. Antagonism of NOS in wild types significantly reduced but did not eliminate LTP (group average reduction of 50%). The residual LTP formed a variable proportion of the total LTP in each cell and was found to be postsynaptic in origin. We found no evidence for silent synapses in this pathway at this age. Finally, application of NO via a donor induced potentiation in layer II/III cells and caused an increase in frequency but not amplitude of miniature EPSPs, again implicating NO in presynaptic plasticity.