Repeated release of transmitter from presynaptic elements depends on stimulus-induced Ca2+influx together with recruitment and priming of synaptic vesicles from different vesicle pools.We have compared three different manipulations of synaptic strength, all of which are knownto increase short-term synaptic efficacy through presynaptic mechanisms, in the glutamatergicCA3-to-CA1 stratum radiatum synapse in the mouse hippocampal slice preparation. Synapticresponses elicited from the readily releasable vesicle pool during low-frequency synapticactivation (0.1 Hz) were significantly enhanced by both the adenylate cyclase activator forskolin,the priming activator β-phorbol-12,13-dibutyrate (PDBu) and 4 mM [Ca2+]o, whereas during 20 Hzstimulation, the same manipulations reduced the time needed to reach the peak and increasedthe magnitude of the resulting frequency facilitation. In contrast, paired-pulse facilitations wereunchanged in the presence of forskolin, decreased by 4 mM [Ca2+]o and essentially abolishedby PDBu. The subsequent delayed response enhancement (DRE) responses, elicited duringcontinuous 20 Hz stimulations and mediated by recruited vesicles, were enhanced by forskolin,essentially unchanged by PDBu and slightly decreased by 4 mM [Ca2+]o. Similar experimentsdone on slices devoid of the vesicle-associated synapsin I and II proteins indicated thatsynapsin I/II-induced enhancements of vesicle recruitment were restricted to Ca2+-inducedfrequency facilitations and forskolin-induced enhancements of the early DRE phase, whereasthe proteins had minor effects during PDBu-treatment and represented constraints on late Ca2+-induced responses. The data indicate that in these glutamatergic synapses, the comparableenhancements of single synaptic responses induced by these biochemical mechanisms canbe transformed during prolonged synaptic stimulation into highly distinct short-term plasticitypatterns, which are partly dependent on synapsins I/II.