Developmental changes in the release probability of thalamocortical synapses : Relevance to silent synapses during critical period

丘脑皮质连接在关键期经历显著的可塑性，越来越多的证据表明，突触后部位沉默突触的激活是这一过程中重要的潜在机制。然而，很少有人知道的突触前性质。在这项研究中，我们研究了释放概率（Pr）的丘脑皮质突触末梢的IV层神经元在发育小鼠桶皮质。采用传统的成对脉冲比（PPR）方法，观察了AMPA和NMDA受体介导的PPR。我们发现，从出生后第4天（P）到P22，NMDA PPR逐渐增加（因此Pr减少），但出乎意料的是，AMPA PPR表现出同时下降。然后，我们使用了另一种方法来评估释放概率，即观察使用MK-801对NMDA介导的EPSC的进行性阻断。通过这种方法，我们能够识别两类释放概率高或低的终端。有趣的是，较高的释放显示在关键时期的概率降低，与NMDA PPR结果一致。我们证实，NMDA和AMPA PPR结果之间的差异是由于沉默的存在，或NMDA，突触，在以前的文献中提出的。通过分析NMDA或AMPA PPR与PPR差异之间的相关性，我们讨论了这样一种假设，即具有瞬时较高释放概率的终末优先出现在沉默突触上。我们的研究结果表明，这些突触前网站也可能有一个积极的作用，可塑性的工作伴随着突触后网站在关键时期。

Thalamocortical connections undergo remarkable plasticity during the critical period and mounting evidence serves to demonstrate that the activation of silent synapses at postsynaptic sites is an important underlying mechanism in this process. However, little is known about the nature of the presynaptic properties. In this study, we examined the release probability (Pr) of thalamocortical synaptic terminals on a layer IV neuron in the developing mouce barrel cortex. Using conventional paired-pulse ratio (PPR) method, both AMPA and NMDA receptor-mediated PPR were observed during development. We found that the NMDA PPR increased gradually (thus reduction of Pr) from postnatal day (P)4 to P22 but, unexpectedly, the AMPA PPR exhibited a simultaneous decrease. We then used an additional method for assessing release probability, the observation of a progressive block of NMDA mediated EPSC using MK-801. With this method, we were able to identify two classes of terminals with high or low probabilities of release. Interestingly, the higher release showed a reduction in probability during the critical period, consistent with the NMDA PPR results. We confirmed that the discrepancy between the NMDA and the AMPA PPR resultes was due to the existence of silent, or NMDA-only, synapses, as suggested in previous literature. By analysing the correlation between the NMDA or AMPA PPR and the PPR discrepancy, we discuss the hypothesis that the terminals with transiently higher probability of release were found preferentially on silent synapses. Our results suggest that these presynaptic sites may also have an active role in plasticity by working concomitantly with postsynaptic sites during the critical period.