Paired-Pulse Plasticity at the Single Release Site Level: An Experimental and Computational Study

Abstract

CA3-CA1 glutamatergic synapses in the hippocampus exhibit a large heterogeneity in release probability (p) and paired-pulse (PP) plasticity, established already in the early neonatal period when the CA3-CA1 connections consist of only a single release site. At such a site two factors decide initial release probability: the number of immediately releasable vesicles (preprimed pool) and the vesicle release probability (P(ves1)). Depletion and replenishment of this pool, an alteration in P(ves), and desensitization of postsynaptic receptors may contribute to PP plasticity. A model based on data from single neonatal CA3-CA1 synapses has been used to address the relative importance of these factors for the heterogeneity in PP plasticity. At a 20 msec PP interval, the PP ratio (P(2)/P(1)) varied from 0.1 to 4.5 among the synapses. At this interval desensitization and replenishment were of little importance. The heterogeneity was explained mostly by the variation in P(ves1), whereas the preprimed pool size was of minor importance. P(ves) altered from the first to the second stimulus such that P(ves2) was rather uniform among the synapses. Its variation thus contributed little to the heterogeneity in PP ratio. The model also shows that the relationship between alterations in release probability and PP ratio is complex. Thus, an increase in release probability can be associated with an increase, a decrease, or no change at all in PP ratio, depending on the original values of P(ves1) and the preprimed pool and on which one of these factors is altered to produce the increase in release probability.