The filtering of input signals carried out at synapses is key to the information processing performed by networks of neurons. Two forms of presynaptic depression, vesicle depletion and G-protein inhibition of Ca2+ channels, can play important roles in the presynaptic processing of information. Using computational models, we demonstrate that these two forms of depression filter information in very different ways. G-protein inhibition acts as a high-pass filter, preferentially transmitting high-frequency input signals to the postsynaptic cell, while vesicle depletion acts as a low-pass filter. We examine how these forms of depression separately and together affect the steady-state postsynaptic responses to trains of stimuli over a range of frequencies. Finally, we demonstrate how differential filtering permits the multiplexing of information within a single impulse train.