Ca²⁺ influx into presynaptic terminals via voltage-dependent Ca²⁺ channels triggers fast neurotransmitter release as well as different forms of synaptic plasticity. Using electrophysiological and genetic techniques we demonstrate that presynaptic Ca²⁺ entry through Ca_v2.3 subunits contributes to the induction of mossy fiber LTP and posttetanic potentiation by brief trains of presynaptic action potentials while they do not play a role in fast synaptic transmission, paired-pulse facilitation, or frequency facilitation. This functional specialization is most likely achieved by a localization remote from the release machinery and by a Ca_v2.3 channel-dependent facilitation of presynaptic Ca²⁺ influx. Thus, the presence of Ca_v2.3 channels boosts the accumulation of presynaptic Ca²⁺ triggering presynaptic LTP and posttetanic potentiation without affecting the low release probability that is a prerequisite for the enormous plasticity displayed by mossy fiber synapses.