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The Journal of Neuroscience, December 14, 2005, 25(50):11655-11665; doi:10.1523/JNEUROSCI.4029-05.2005

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Cellular/Molecular
The Influence of Multivesicular Release and Postsynaptic Receptor Saturation on Transmission at Granule Cell to Purkinje Cell Synapses

Kelly A. Foster, ^* John J. Crowley, ^* and Wade G. Regehr

Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115

The properties of a synapse are crucially dependent on whether an action potential can trigger the release of multiple vesicles at an individual release site [multivesicular release (MVR)] and whether fusion of a single vesicle leads to receptor saturation. MVR and receptor saturation both occur at some high p synapses, but it is not known whether they also occur at low p synapses. Here we examine this issue at the low p synapse between parallel fibers and Purkinje cells using the low-affinity antagonist DGG (-D-glutamylglycine) to relieve AMPA receptor saturation. We find that the presence of MVR and receptor saturation at this synapse alters the calcium dependence of synaptic transmission and reduces the extent of facilitation. These findings establish that MVR and postsynaptic receptor saturation can influence transmission even at synapses with a low initial probability of release and suggest that these properties may be common at synapses in the mammalian brain.

Key words: synaptic plasticity; cerebellum; saturation; multivesicular release; facilitation; calcium dependence; parallel fiber; low-affinity antagonist

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Received Sep 22, 2005; revised October 28, 2005; accepted October 29, 2005.

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