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

Abstract

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.

Adaptation of Granule Cell to Purkinje Cell Synapses to High-Frequency Transmission

“…In 16 of 18 pairs, the time course of facilitation could be fitted by a single exponential. Figure 1 D, in which PPRs were averaged (n ϭ 18; PPR A2/A1 at 50 Hz ϭ 1.7 Ϯ 0.14, PPR A2/A1 at 100 Hz ϭ 2.1 Ϯ 0.15; ϭ 29.4 Ϯ 8.49 ms; [Ca 2ϩ ] e ϭ 2.5 mM), shows that facilitation is modest and decays more quickly than reported previously using compound stimulation in the molecular layer (Atluri and Regehr, 1996;Foster et al, 2005). Because averaging PPR across pairs gives the same importance to small, noisy connections as to strong connections, we also averaged the mean amplitude from all pairs and then plotted the ratio of these means as a function of interstimulus interval.…”

Fast Synaptic Vesicle Reuse Slows the Rate of Synaptic Depression in the CA1 Region of Hippocampus

“…These results show that rapid vesicle reuse provides a viable mechanism to increase neurotransmitter output in the face of demand in addition to the well documented mechanisms such as neurotransmitter spillover from multiple release sites (Telgkamp et al, 2004). The prevalence of multivesicular release in several types of central synapses may also be a critical factor, which could place significant demands on vesicle supply (Wadiche and Jahr, 2001;Foster et al, 2005;Christie and Jahr, 2006). Therefore, it will be interesting to use the approach we outlined in this study to probe the dynamics of vesicle recycling in other brain regions with rapid time resolution.…”

Short-Term Presynaptic Plasticity

“…For granule cell -to -Purkinje cell synapses, facilitation is sixfold in low Ca e and much smaller in high Ca e (Fig. 2B, red trace) (Foster et al 2005). At synapses with such a low probability of release it can be exceedingly difficult to observe paired-pulse depression.…”