Active Zones and the Readily Releasable Pool of Synaptic Vesicles at the Neuromuscular Junction of the Mouse

Ruiz, Rocío; Cano, Raquel; Casañas, Juan José; Gaffield, Michael A.; Betz, William J.; Tabares, Lucı́a

doi:10.1523/jneurosci.4663-10.2011

Cited by 100 publications

(126 citation statements)

References 41 publications

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“…It is also noted that the present study was performed on juvenile rats (11-17 d of age) and that the RRP may vary with age. On the other hand, our study is consistent with functional results obtained at the calyx of Held with calcium uncaging (32); at the neuromuscular junction with presynaptic AP trains (39); and, notably, with quantitative EM at both preparations (4,40). In each of these cases, the RRP was interpreted as the number of vesicles bound at specific docking sites, with each synaptic release site having only a few (two to six) docking sites (Fig.…”

Section: Comparison Of the Present Results With Rrp Estimates In Othersupporting

confidence: 91%

Readily releasable pool of synaptic vesicles measured at single synaptic contacts

Trigo

Sakaba

Ogden

et al. 2012

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

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To distinguish between different models of vesicular release in brain synapses, it is necessary to know the number of vesicles of transmitter that can be released immediately at individual synapses by a high-calcium stimulus, the readily releasable pool (RRP). We used direct stimulation by calcium uncaging at identified, singlesite inhibitory synapses to investigate the statistics of vesicular release and the size of the RRP. Vesicular release, detected as quantal responses in the postsynaptic neuron, showed an unexpected stochastic variation in the number of quanta from stimulus to stimulus at high intracellular calcium, with a mean of 1.9 per stimulus and a maximum of three or four. The results provide direct measurement of the RRP at single synaptic sites. They are consistent with models in which release proceeds from a small number of vesicle docking sites with an average occupancy around 0.7.release site | exocytosis | interneurons | cerebellum

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Section: Comparison Of the Present Results With Rrp Estimates In Othersupporting

confidence: 91%

Readily releasable pool of synaptic vesicles measured at single synaptic contacts

Trigo

Sakaba

Ogden

et al. 2012

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

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“…These data indicate that each AZ harbors approximately one release-ready vesicle under resting conditions. Interestingly, a recent study at the NMJ of the mouse found approximately two release-ready vesicles per AZ with similar techniques (Ruiz et al, 2011). In our experiments in which presynaptic strengthening was induced, the number of AZs estimated with confocal and STED imaging remained constant, but the number of functionally determined release-ready vesicles doubled, indicating that a presynaptically strengthened Drosophila AZ harbors approximately two release-ready vesicles (Fig.…”

Section: Discussionsupporting

confidence: 75%

Rapid Active Zone Remodeling during Synaptic Plasticity

Weyhersmüller

Hallermann²,

Wagner³

et al. 2011

J. Neurosci.

169

226

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How can synapses change the amount of neurotransmitter released during synaptic plasticity? Although release in general is intensely investigated, its determinants during plasticity are still poorly understood. As a model for plastic strengthening of synaptic release, we here use the well-established presynaptic homeostatic compensation during interference with postsynaptic glutamate receptors at the Drosophila neuromuscular junction. Combining short-term plasticity analysis, cumulative EPSC analysis, fluctuation analysis, and quantal short-term plasticity modeling, we found an increase in the number of release-ready vesicles during presynaptic strengthening. High-resolution light microscopy revealed an increase in the amount of the active zone protein Bruchpilot and an enlargement of the presynaptic cytomatrix structure. Furthermore, these functional and structural alterations of the active zone were not only observed after lifelong but already after minutes of presynaptic strengthening. Our results demonstrate that presynaptic plasticity can induce active zone remodeling, which regulates the number of release-ready vesicles within minutes.

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“…At giant synapses such as the skeletal muscle neuromuscular junction or at the calyx of Held, efficient methods have been developed to extract vesicular release rates using a template reflecting miniature currents (the deconvolution approach; Neher and Sakaba, 2003;Ruiz et al, 2011). These methods must deal with complicating factors linked with variability of quantal shape among synaptic sites, with receptor saturation and desensitization, with cross talk among neighboring release sites, and with slow diffusion of the neurotransmitter out of the synaptic cleft.…”

Section: Introductionmentioning

confidence: 99%

Counting Vesicular Release Events Reveals Binomial Release Statistics at Single Glutamatergic Synapses

et al. 2016

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Many central glutamatergic synapses contain a single presynaptic active zone and a single postsynaptic density. However, the basic functional properties of such "simple synapses" remain unclear. One important step toward understanding simple synapse function is to analyze the number of synaptic vesicles released in such structures per action potential, but this goal has remained elusive until now. Here, we describe procedures that allow reliable vesicular release counting at simple synapses between parallel fibers and molecular layer interneurons of rat cerebellar slices. Our analysis involves local extracellular stimulation of single parallel fibers and deconvolution of resulting EPSCs using quantal signals as template. We observed a reduction of quantal amplitudes (amplitude occlusion) in pairs of consecutive EPSCs due to receptor saturation. This effect is larger (62%) than previously reported and primarily reflects receptor activation rather than desensitization. In addition to activation-driven amplitude occlusion, each EPSC reduces amplitudes of subsequent events by an estimated 3% due to cumulative desensitization. Vesicular release counts at simple synapses follow binomial statistics with a maximum that varies from 2 to 10 among experiments. This maximum presumably reflects the number of docking sites at a given synapse. These results show striking similarities, as well as significant quantitative differences, with respect to previous results at simple GABAergic synapses.

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Active Zones and the Readily Releasable Pool of Synaptic Vesicles at the Neuromuscular Junction of the Mouse

Cited by 100 publications

References 41 publications

Readily releasable pool of synaptic vesicles measured at single synaptic contacts

Readily releasable pool of synaptic vesicles measured at single synaptic contacts

Rapid Active Zone Remodeling during Synaptic Plasticity

Counting Vesicular Release Events Reveals Binomial Release Statistics at Single Glutamatergic Synapses

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