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J Physiol Volume 586, Number 13, 3129-3146, July 1, 2008 DOI: 10.1113/jphysiol.2008.152124
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NEUROSCIENCE

Interactions between multiple sources of short-term plasticity during evoked and spontaneous activity at the rat calyx of Held

 Matthias H. Hennig1,4, Michael Postlethwaite2,3, Ian D. Forsythe3 and Bruce P. Graham4

1 ANC, School of Informatics, University of Edinburgh, 5 Forrest Hill, Edinburgh EH1 2QL, UK
2 Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, UK
3 MRC Toxicology Unit, University of Leicester, Leicester LEI 9HN, UK
4 Computing Science and Mathematics, University of Stirling, Stirling FK9 4LA, UK

Sustained activity at most central synapses is accompanied by a number of short-term changes in synaptic strength which act over a range of time scales. Here we examine experimental data and develop a model of synaptic depression at the calyx of Held synaptic terminal that combines many of these mechanisms (acting at differing sites and across a range of time scales). This new model incorporates vesicle recycling, facilitation, activity-dependent vesicle retrieval and multiple mechanisms affecting calcium channel activity and release probability. It can accurately reproduce the time course of experimentally measured short-term depression across different stimulus frequencies and exhibits a slow decay in EPSC amplitude during sustained stimulation. We show that the slow decay is a consequence of vesicle release inhibition by multiple mechanisms and is accompanied by a partial recovery of the releasable vesicle pool. This prediction is supported by patch-clamp data, using long duration repetitive EPSC stimulation at up to 400 Hz. The model also explains the recovery from depression in terms of interaction between these multiple processes, which together generate a stimulus-history-dependent recovery after repetitive stimulation. Given the high rates of spontaneous activity in the auditory pathway, the model also demonstrates how these multiple interactions cause chronic synaptic depression under in vivo conditions. While the magnitude of the depression converges to the same steady state for a given frequency, the time courses of onset and recovery are faster in the presence of spontaneous activity. We conclude that interactions between multiple sources of short-term plasticity can account for the complex kinetics during high frequency stimulation and cause stimulus-history-dependent recovery at this relay synapse.

(Received 4 February 2008; accepted after revision 30 April 2008; first published online 1 May 2008)
Corresponding author M. H. Hennig: ANC, School of Informatics, University of Edinburgh, 5 Forrest Hill, Edinburgh, EH1 2QL, UK. Email: mhennig{at}inf.ed.ac.uk






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