Interaction between short-term facilitation and depression at the Calyx of Held

JUAN D. GOUTMAN; MARTIN MÜLLER; RALF SCHNEGGENBURGER

Göttingen, Alemania

Congreso; 8th. Göttingen German Neuroscience Society Meeting; 2009

Repetitive stimulation of the calyx of Held synapse in slices typically results in a decrease of synaptic strength, so that this synapse has been classified as a "depressing" synapse. In vivo, auditory brainstem neurons fire continuously at elevated rates (tens of Hertz), even in the absence of sound, and sound stimuli lead to a further increase in firing frequency. Therefore, classical stimulation protocols that have been employed to probe short-term plasticity – high-frequency trains that are applied after relatively long pauses (~ 10 - 40 sec) – might be inappropriate to capture the full range of short-term dynamics of these auditory synapses. Here, we investigated short-term plasticity of the calyx of Held with a protocol designed to comprise the basic characteristics of the synapse’s physiological sound-evoked stimulus pattern: a ´low´-frequency (20 Hz) ´conditioning´ train, which was instantly followed by a high-frequency (200 Hz) train. As expected, EPSCs showed depression during the 20 Hz conditioning train. Surprisingly, synaptic transmission was strongly (~ twofold) facilitated during the onset of 200 Hz trains that were conditioned by preceding 20 Hz trains. Direct presynaptic whole-cell recordings and Ca2+ imaging showed that this facilitation was not mediated by Ca2+-current facilitation, and that facilitation depended on the build-up of residual Ca2+ during the first few stimuli of the high-frequency train. The conditioning 20 Hz train depleted the readily-releasable vesicle pool by ~ 50 %. Interestingly, we found that the release kinetics of the remaining pool of fast-releasable vesicles (FRP) was notably slowed (by about 1.5 fold). This implies that a decrease in the release probability (p) of FRP vesicles contributes to synaptic depression. Preliminary results obtained from presynaptic Ca2+ uncaging experiments also revealed a slowing of the release kinetics of FRP vesicles, indicating that the reduced p is caused by an intrinsic mechanism. We hypothesize that vesicles with a reduced intrinsic p are more prone to the effects of short-term facilitation, and therefore cause a marked transient overshoot in synaptic strength during the onset of a high-frequency trains under near-physiological conditions.