Reluctant vesicles coaxed into the limelight

Synapses respond to brief, repetitive stimulation with synaptic depression when initial transmitter release probability is high. Vesicle depletion has been a long-standing hypothesis for depression, but results unexplained by the depletion hypothesis have been nagging. In this issue of Neuron, Xu and Wu show that, under some conditions, calcium current inactivation explains stimulus-dependent depression at the calyx of Held.