Heterogeneity of Release Probability, Facilitation, and Depletion at Central Synapses

Abstract

Previous studies of short-term plasticity in central nervous systems synapses have largely focused on average synaptic properties. In this study, we use recordings from putative single synaptic release sites in hippocampal slices to show that significant heterogeneity exists in facilitation and depletion among synapses. In particular, the amount of paired-pulse facilitation is inversely related to the initial release probability of the synapse. We also examined depletion at individual synapses using high frequency stimulation, and estimated the size of the readily releasable vesicle pool, which averaged 5.0 +/- 3.0 quanta (n = 13 synapses). In addition, these experiments demonstrate that the release probability at a synapse is directly correlated with the size of its readily releasable vesicle pool.

Quantal Size Is Independent of the Release Probability at Hippocampal Excitatory Synapses

“…It is generally agreed that an increase in the P r occurs during facilitation; however, it is still debated whether the increase in P r is solely responsible for the facilitation or whether postsynaptic modifications also take place. Several studies reported an exclusive presynaptic alteration (Gulyas et al, 1993;Stevens and Wang, 1995;Dobrunz and Stevens, 1997;Hanse and Gustafsson, 2001;Silver et al, 2003;Chen et al, 2004;Lawrence et al, 2004), but evidence has also been published supporting significant postsynaptic modifications, including an increased quantal size after multivesicular release (Oertner et al, 2002;Conti and Lisman, 2003) or removing the polyamine block from certain postsynaptic glutamate receptors (Rozov and Burnashev, 1999). To some extent, the reason for the discrepancy is likely attributable to differences in experimental approaches, such as the preparations, the age of the animals, and the identity of the synapses examined.…”

“…Such a change in the transmitter concentration waveform may be interpreted as the consequence of multivesicular release. On the other hand, several studies applied minimal extracellular stimulations to identify single release sites and reached the conclusion that q is independent of P r (Stevens and Wang, 1995;Dobrunz and Stevens, 1997;Hanse and Gustafsson, 2001). A potential drawback of these experiments is the subselection of certain fibers, and therefore the conclusions may hold true only for a minor sub- Fig.…”

“…This led to the formulation of the one-vesicle hypothesis (Korn et al, 1994): either no vesicle or only one vesicle is released at one release site after the arrival of a presynaptic action potential. Several recent studies tested the one-release site, one-vesicle hypothesis at mammalian central synapses and came to various conclusions (Auger et al, 1998;Wadiche and Jahr, 2001;Oertner et al, 2002;Schneggenburger et al, 2002;Conti and Lisman, 2003) (but see Gulyas et al, 1993;Stevens and Wang, 1995;Dobrunz and Stevens, 1997;Hanse and Gustafsson, 2001;Silver et al, 2003;Lawrence et al, 2004). As mentioned above, the discrepancy may be the consequence of technical differences, most notably distinctions in the way presynaptic axons were stimulated.…”

Vesicle number does not predict postsynaptic measures of miniature synaptic activity frequency in cultured cortical neurons

“…These findings contrast with a recent hypothesis that the readily releasable pool, which determines action potential-evoked release probability, may be equivalent to the number of docked vesicles. 9,38,41 These results, although preliminary, suggest that miniature release probability may be controlled by factors in addition to the number of morphologically docked vesicles. Conceivably, vesicles that are subject to spontaneous release may represent a subset of the morphologically docked vesicles that have been further "primed" through a mechanism that cannot currently be resolved at the ultrastructural level.…”

Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase

“…The RRP is thought to correspond to the number of synaptic vesicles morphologically docked to the presynaptic membrane that can be released (Rosenmund and Stevens, 1996;Dobrunz and Stevens, 1997). Synaptic vesicles in the RP are organized in clusters in which the vesicles are reversibly linked to the actin-based cytoskeleton by a family of abundant synaptic vesicle-associated phosphoproteins, the synapsins Ceccaldi et al, 1995;Pieribone et al, 1995;Kuromi and Kidokoro, 1998).…”