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Fast vesicle reloading and a large pool sustain high bandwidth transmission at a central synapse


What limits the rate at which sensory information can be transmitted across synaptic connections in the brain? High-frequency signalling is restricted to brief bursts at many central excitatory synapses1,2, whereas graded ribbon-type synapses can sustain release3 and transmit information4 at high rates. Here we investigate transmission at the cerebellar mossy fibre terminal, which can fire at over 200 Hz for sustained periods in vivo5, yet makes few synaptic contacts onto individual granule cells6. We show that connections between mossy fibres and granule cells can sustain high-frequency signalling at physiological temperature. We use fluctuation analysis7 and pharmacological block of desensitization to identify the quantal determinants of short-term plasticity and combine these with a short-term plasticity model and cumulative excitatory postsynaptic current analysis to quantify the determinants of sustained high-frequency transmission. We show that release is maintained at each release site by rapid reloading of release-ready vesicles from an unusually large releasable pool of vesicles8 (300 per site). Our results establish that sustained vesicular release at high rates is not restricted to graded ribbon-type synapses and that mossy fibres are well suited for transmitting broad-bandwidth rate-coded information to the input layer of the cerebellar cortex.

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Figure 1: Frequency dependence of transmission at the MF–GC synapse.
Figure 2: Quantal determinants of short-term plasticity at MF–GC connections.
Figure 3: Recovery from depression and facilitation at MF–GC synapses.
Figure 4: Time course of vesicle reloading and releasable pool size.


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We thank D. DiGregorio and I. Kleppe for discussions; and D. Attwell, D. DiGregorio, I. Kleppe, T. Nielsen, A. Roth and V. Steuber for comments on the manuscript. This work was supported by The Wellcome Trust and the European Community. R.A.S. is in receipt of a Wellcome Trust Senior Fellowship.

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Correspondence to R. Angus Silver.

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Supplementary Notes

This file contains the Supplementary Methods (Determining quantal parameters with MPFA and CV analysis; short-term plasticity model for extracting the time course of recovery from presynaptic depression; and serial and parallel models of vesicle reloading at the MF) and Supplementary Figure 1 (Short-term plasticity during pharmacological block of AMPAR desensitisation.).

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Saviane, C., Silver, R. Fast vesicle reloading and a large pool sustain high bandwidth transmission at a central synapse. Nature 439, 983–987 (2006).

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