High- and Low-Mobility Stages in the Synaptic Vesicle Cycle

Kamin, Dirk; Lauterbach, Marcel A.; Westphal, Volker; Keller, Jan; Schönle, Andreas; Hell, Stefan W.; Rizzoli, Silvio O.

doi:10.1016/j.bpj.2010.04.054

Cited by 73 publications

(124 citation statements)

References 40 publications

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“…These data are in accordance with the finding that electrical stimulation has no influence on the mobility of single SVs in short timeframes (Kamin et al, 2010), although a more careful evaluation with longer timeframes and/or stimulation protocols might be required, because this issue is still debated (Fisher-Lavie et al, 2011). Nevertheless, our results indicate that the population of delocalized SVs observed in TKO synapses includes exocytosis-competent SVs.…”

Section: Discussionsupporting

confidence: 81%

“…It is noteworthy that acute TTX block does not revert the dispersion phenotype of TKO terminals, although it has been reported to decrease SV motion (Kamin et al, 2010). The most obvious explanation for this observation is that the mechanism(s) constraining SVs at nerve terminals in the absence of Syns has a low efficiency and requires a long time to revert the altered phenotype.…”

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confidence: 80%

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Synapsins Contribute to the Dynamic Spatial Organization of Synaptic Vesicles in an Activity-Dependent Manner

et al. 2012

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The precise subcellular organization of synaptic vesicles (SVs) at presynaptic sites allows for rapid and spatially restricted exocytotic release of neurotransmitter. The synapsins (Syns) are a family of presynaptic proteins that control the availability of SVs for exocytosis by reversibly tethering them to each other and to the actin cytoskeleton in a phosphorylation-dependent manner. Syn ablation leads to reduction in the density of SV proteins in nerve terminals and increased synaptic fatigue under high-frequency stimulation, accompanied by the development of an epileptic phenotype. We analyzed cultured neurons from wild-type and Syn I,II,III Ϫ/Ϫ triple knock-out (TKO) mice and found that SVs were severely dispersed in the absence of Syns. Vesicle dispersion did not affect the readily releasable pool of SVs, whereas the total number of SVs was considerably reduced at synapses of TKO mice. Interestingly, dispersion apparently involved exocytosis-competent SVs as well; it was not affected by stimulation but was reversed by chronic neuronal activity blockade. Altogether, these findings indicate that Syns are essential to maintain the dynamic structural organization of synapses and the size of the reserve pool of SVs during intense SV recycling, whereas an additional Syn-independent mechanism, whose molecular substrate remains to be clarified, targets SVs to synaptic boutons at rest and might be outpaced by activity.

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Section: Discussionsupporting

confidence: 81%

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confidence: 80%

Synapsins Contribute to the Dynamic Spatial Organization of Synaptic Vesicles in an Activity-Dependent Manner

et al. 2012

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“…They would simply stay linked to other vesicles and/or to the cytoskeleton (perhaps via synapsin), at tens or hundreds of nanometers from the active zones. This hypothesis is in agreement with two recent findings on vesicle mobility and recycling: first, only a small pool of vesicles is mobile in cultured hippocampal synapses, with all other vesicles immobile ["fixed" (33)]. The fixed vesicles did not become more mobile upon physiological stimulation, suggesting that they may not be involved in neurotransmitter release and recycling under normal circumstances (see also ref.…”

Section: Discussionsupporting

confidence: 81%

A small pool of vesicles maintains synaptic activity in vivo

Denker

Bethani

Kröhnert

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Chemical synapses contain substantial numbers of neurotransmitter-filled synaptic vesicles, ranging from approximately 100 to many thousands. The vesicles fuse with the plasma membrane to release neurotransmitter and are subsequently reformed and recycled. Stimulation of synapses in vitro generally causes the majority of the synaptic vesicles to release neurotransmitter, leading to the assumption that synapses contain numerous vesicles to sustain transmission during high activity. We tested this assumption by an approach we termed cellular ethology, monitoring vesicle function in behaving animals (10 animal models, nematodes to mammals). Using FM dye photooxidation, pHluorin imaging, and HRP uptake we found that only approximately 1-5% of the vesicles recycled over several hours, in both CNS synapses and neuromuscular junctions. These vesicles recycle repeatedly, intermixing slowly (over hours) with the reserve vesicles. The latter can eventually release when recycling is inhibited in vivo but do not seem to participate under normal activity. Vesicle recycling increased only to ≈5% in animals subjected to an extreme stress situation (frog predation on locusts). Synapsin, a molecule binding both vesicles and the cytoskeleton, may be a marker for the reserve vesicles: the proportion of vesicles recycling in vivo increased to 30% in synapsin-null Drosophila. We conclude that synapses do not require numerous reserve vesicles to sustain neurotransmitter release and thus may use them for other purposes, examined in the accompanying paper.pools | styryl dyes | vesicle cycle | shibire |

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“…While not yet entirely understood, they probably involve, among many others, actin (Cingolani and Goda, 2008), Synapsins (Cesca et al, 2010), trans-synaptic complexes (Linhoff et al, 2009;Brigidi and Bamji, 2011), efficient endocytosis mechanisms (Kamin et al, 2010), as well as particular protein kinases and phosphatases (Lee et al, 2008;Kim and Ryan, 2010;reviewed in Pechstein and Shupliakov, 2010;. Whatever these mechanisms might be, our findings indicate that they collectively act to restore synapse-specific set points.…”

Section: Use Dependence Of Presynaptic Tenacitymentioning

confidence: 66%

Use Dependence of Presynaptic Tenacity

Fisher-Lavie

Zeidan²,

Stern³

et al. 2011

J. Neurosci.

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Recent studies indicate that synaptic vesicles (SVs) are continuously interchanged among nearby synapses at very significant rates. These dynamics and the lack of obvious barriers confining synaptic vesicles to specific synapses would seem to challenge the ability of synapses to maintain a constant amount of synaptic vesicles over prolonged time scales. Moreover, the extensive mobilization of synaptic vesicles associated with presynaptic activity might be expected to intensify this challenge. Here we examined the ability of individual presynaptic boutons of rat hippocampal neurons to maintain their synaptic vesicle content, and the degree to which this ability is affected by continuous activity. We found that the synaptic vesicle content of individual boutons belonging to the same axons gradually changed over several hours, and that these changes occurred independently of activity. Intermittent stimulation for 1 h accelerated rates of vesicle pool size change. Interestingly, however, following stimulation cessation, vesicle pool size change rates gradually converged with basal change rates. Over similar time scales, active zones (AZs) exhibited substantial remodeling; yet, unlike synaptic vesicles, AZ remodeling was not affected by the stimulation paradigms used here. These findings indicate that enhanced activity levels can increase synaptic vesicle redistribution among nearby synapses, but also highlight the presence of forces that act to restore particular set points in terms of SV contents, and support a role for active zones in preserving such set points. These findings also indicate, however, that neither AZ size nor SV content set points are particularly stable, questioning the long-term tenacity of presynaptic specializations.

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High- and Low-Mobility Stages in the Synaptic Vesicle Cycle

Cited by 73 publications

References 40 publications

Synapsins Contribute to the Dynamic Spatial Organization of Synaptic Vesicles in an Activity-Dependent Manner

Synapsins Contribute to the Dynamic Spatial Organization of Synaptic Vesicles in an Activity-Dependent Manner

A small pool of vesicles maintains synaptic activity in vivo

Use Dependence of Presynaptic Tenacity

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