Modular competition driven by NMDA receptor subtypes in spike-timing-dependent plasticity
Modular competition driven by NMDA receptor subtypes in spike-timing-dependent plasticity
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DOI：
10.1152/jn.00860.2006
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发表时间：
2007-04-01
影响因子：
2.5
通讯作者：
Bi, Guo-Qiang
中科院分区：
文献类型：
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作者：
Gerkin, Richard C.;Lau, Pak-Ming;Bi, Guo-Qiang
N-甲基-D-天冬氨酸受体（NMDARs）在将神经元活动模式转换为突触强度变化中起关键作用。然而，它们如何介导这种转导以响应生理刺激仍然是难以捉摸的。特别是，它已被争论是否不同的NMDAR亚型发挥相反的信号作用，在突触可塑性。使用穿孔膜片钳记录从对突触连接的海马神经元在分离的海马文化，我们发现，尖峰时间依赖性增强诱导配对前和突触后尖峰需要激活的快组件的NMDAR电流，这可能是由NR2A-含有NMDARs（NR2A-NRs）介导的。与此相反，尖峰时间依赖性抑郁症需要一个缓慢的组件NMDAR电流携带的NR2B-含有NMDAR（NR2BNR）。CV分析表明，这种抑郁症的位点主要是突触前的细胞对强大的突触连接，而较弱的突触表现出没有明确的偏好前或突触后表达。这种抑郁症并没有显着减少CB1受体的拮抗作用，相反，尖峰时间依赖性抑郁症的新皮层，需要突触前CB1信号。阻断NR2B-NRs后，含有增强和抑制尖峰定时成分的尖峰三联体诱导净增强。然而，当假定的NR2A-NR人口被抑制，这些尖峰三联体导致抑郁症或没有净变化，这取决于时间顺序的尖峰定时组件。这些结果意味着一个动态的信号模块之间的竞争，可以有偏见的差异拮抗NMDAR亚型在诱导尖峰时间依赖性可塑性。使用一个简单的模型，我们表明，这样一个模块化的竞争概括了我们的观察。
N-methyl-D-aspartate receptors (NMDARs) play a critical role in transducing neuronal activity patterns into changes in synaptic strength. However, how they mediate this transduction in response to physiological stimuli has remained elusive. In particular, it has been debated whether different NMDAR subtypes play opposing signaling roles in synaptic plasticity. Using perforated patch-clamp recordings from pairs of synaptically connected glutamatergic neurons in dissociated hippocampal culture, we found that spike-timing-dependent potentiation induced by pairing pre- and postsynaptic spikes required the activation of a fast component of NMDAR current that is likely to be mediated by NR2A-containing NMDARs (NR2A-NRs). In contrast, spike-timing-dependent depression required a slow component of NMDAR current carried by NR2B-containing NMDARs (NR2BNRs). CV analysis showed that the locus of this depression was primarily presynaptic in pairs of cells making strong synaptic connections, whereas weaker synapses showed no clear preference for pre- or postsynaptic expression. This depression was not significantly reduced by antagonism of the CB1 receptor, in contrast to spike-timing-dependent depression in the neocortex that requires presynaptic CB1 signaling. With blockade of NR2B-NRs, spike triplets that contained both potentiating and depressing spike-timing components induced net potentiation. However, when the putative NR2A-NR population is inhibited, these spike triplets resulted in either depression or no net change, depending on the temporal order of the spike-timing components. These results imply a dynamic competition between signaling modules that can be biased by differentially antagonizing NMDAR subtypes during the induction of spike-timing-dependent plasticity. Using a simple model, we show that such a modular competition recapitulates our observations.