Skipped-stimulus approach reveals that short-term plasticity dominates synaptic strength during ongoing activity.

All synapses show activity-dependent changes in strength, which affect the fidelity of postsynaptic spiking. This is particularly important at auditory nerve synapses, where the presence and timing of spikes carry information about a sound's structure, which must be passed along for proper processing. However, it is not clear how synaptic plasticity influences spiking during ongoing activity. Under these conditions, conventional analyses erroneously suggest that synaptic plasticity has no influence on EPSC amplitude or spiking. Therefore, we developed new approaches to study how ongoing activity influences synaptic strength, using voltage- and current-clamp recordings from bushy cells in brain slices from mouse anteroventral cochlear nucleus. We applied identical trains of stimuli, except for one skipped stimulus, and found that EPSC amplitude was affected for 60 ms following a skipped stimulus. We further showed that the initial probability of release, calcium-dependent mechanisms of recovery, and desensitization all play a role even during ongoing activity. Current-clamp experiments indicated that these processes had a significant effect on postsynaptic spiking, as did the refractory period to a smaller extent. Thus short-term plasticity has real, important functional consequences.