Postsynaptic Action Potentials Are Required for Nitric-Oxide-Dependent Long-Term Potentiation in CA1 Neurons of Adult GluR1 Knock-Out and Wild-Type Mice

Postsynaptic Action Potentials Are Required for Nitric-Oxide-Dependent Long-Term Potentiation in CA1 Neurons of Adult GluR1 Knock-Out and Wild-Type Mice
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DOI:
10.1523/jneurosci.3984-08.2008
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发表时间:
2008-12-24
影响因子:
5.3
通讯作者:
Fox, Kevin
Fox, Kevin
中科院分区:
医学1区
文献类型:
--
作者:
Phillips, Keith G.;Hardingham, Neil R.;Fox, Kevin

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新皮层长时程增强(LTP)由突触前和突触后成分组成,分别依赖于一氧化氮(NO)和AMPA受体的GluR 1亚基。在这项研究中,我们发现,海马LTP,θ-突发刺激诱导成熟(> 8周龄)GluR 1基因敲除小鼠几乎完全是NO依赖性的,并涉及α剪接变体的NO合成酶-1和NO合成酶-3亚型的NO合成酶。θ-爆发诱导的LTP也部分依赖于野生型小鼠,并作出了类似的50%的增强破伤风后2小时。θ-突发刺激可靠地产生突触后尖峰,包括复杂尖峰的高概率。用细胞内QX 314或局部TTX应用抑制突触后体细胞尖峰可以防止GluR 1敲除小鼠的LTP,也可以阻断野生型LTP的NO组分。我们的结论是,θ-突发刺激是特别适合于产生突触后体细胞尖峰所需的NO依赖性LTP。
Neocortical long-term potentiation (LTP) consists of both presynaptic and postsynaptic components that rely on nitric oxide ( NO) and the GluR1 subunit of theAMPAreceptor, respectively. In this study, we found that hippocampal LTP, induced by theta-burst stimulation in mature (> 8-week-old) GluR1 knock-out mice was almost entirely NO dependent and involved both the alpha splice variant of NO synthase-1 and the NO synthase-3 isoforms of NO synthase. Theta-burst induced LTP was also partly NO-dependent in wild-type mice and made up similar to 50% of the potentiation 2 h after tetanus. Theta-burst stimulation reliably produced postsynaptic spikes, including a high probability of complex spikes. Inhibition of postsynaptic somatic spikes with intracellular QX314 or local TTX application prevented LTP in the GluR1 knock-out mice and also blocked the NO component of LTP in wild types. We conclude that theta-burst stimulation is particularly well suited to producing the postsynaptic somatic spikes required for NO-dependent LTP.