Information transfer within neuronal networks requires the precise coordination of distinct neuronal populations within a given circuit. Evidence from a variety of central pathways indicates that such coordination is mediated in part by the ability of neurons to differentially regulate release properties at functionally divergent presynaptic elements along their individual axons according to the identity of the postsynaptic cell being innervated. Recent findings have revealed the cellular mechanisms by which central afferents modify release properties at individual presynaptic sites independent of neighboring terminals. Such autonomy of presynaptic regulation enables target-cell-dependent short-term and long-term synaptic plasticity and ensures that distinct features of afferent activity are relayed to divergent target-cell populations.