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

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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.