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

丘脑皮质连接在这一关键期经历了显着的可塑性，越来越多的证据表明，突触后静默突触的激活是这一过程中的一个重要机制。然而，人们对突触前特性的性质知之甚少。在这项研究中，我们检测了发育中的小鼠桶状皮质第IV层神经元上丘脑皮质突触终末的释放概率(Pr)。用传统的配对脉冲比率(PPR)方法，在发育过程中观察到AMPA和NMDA受体介导的PPR。我们发现，从出生后第4天到第22天，NMDA PPR逐渐增加(Pr降低)，而AMPA PPR却同时下降。然后，我们使用了另一种评估释放概率的方法，即使用MK-801观察NMDA介导的EPSC的进行性阻断。通过这种方法，我们能够识别出释放概率高或低的两类终端。有趣的是，较高的释放量显示出关键期内概率的降低，这与NMDA PPR结果一致。我们证实，NMDA和AMPA PPR结果之间的差异是由于存在沉默的或仅有NMDA的突触，如以前的文献所述。通过分析NMDA或AMPA PPR与PPR差异的相关性，我们讨论了这样一种假设，即瞬时释放概率较高的终末优先发现在无声突触上。我们的结果表明，这些突触前部位也可能通过在关键期与突触后部位一起工作而在可塑性中发挥积极作用。

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.