Release kinetics, quantal parameters and their modulation during short‐term depression at a developing synapse in the rat CNS

Taschenberger, Holger; Scheuss, Volker; Neher, Erwin

doi:10.1113/jphysiol.2005.093468

Cited by 108 publications

(159 citation statements)

References 79 publications

(157 reference statements)

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“…It is also in accord with an earlier report of a decrease with age in the number of docked SVs at calyx AZs (28). Finally, the finding of a decrease in release probability is consistent with previous results at several types of central synapses (47)(48)(49)(50); but see 32). In the calyx of Held this decrease is associated with a shortening of the AP waveform (51) and a consequent decrease of Ca 2+ entry (34).…”

Section: Discussionsupporting

confidence: 83%

“…This fact is due to the combination of three separate effects: a decrease of the quantal size; a decrease of N D ; and a decrease in the probability of release at each docking site. Our finding of a decrease in quantal size between 2 wk and 4 wk is consistent with a similar decrease at MLI-MLI synapses (47) but contrasts with the reported increase at the calyx of Held between 1 wk and 2 wk (48). The finding of a decrease of N D is consistent with our finding of a decrease in the quantal size, given the correspondence between the sizes of pre-and postsynaptic structures at simple synapses (46).…”

Section: Discussionsupporting

confidence: 81%

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Numbers of presynaptic Ca ²⁺ channel clusters match those of functionally defined vesicular docking sites in single central synapses

Miki

Kaufmann

Malagón

et al. 2017

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

107

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Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such "simple synapses" indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Ca v 2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Ca v 2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1-10) and 2.03 at 4 wk (range: 1-4), whereas the mean numbers of Ca v 2.1 clusters were 2.84 at 2 wk (range: 1-8) and 2.37 at 4 wk (range: 1-5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm 2 to 0.0234 μm 2 ), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels.neurotransmitter release | active zone | calcium channel | release site | parallel fiber I n presynaptic terminals, the active zone (AZ) represents a highly specialized structure allowing the binding and Ca 2+ -dependent release of synaptic vesicles (SVs) (1). Fluctuation analysis of synaptic signals suggests the presence of one or several functional units per AZ (2, 3). These units are either called "release sites" or "docking sites," and their number per AZ represents the maximum SV output that this structure can provide per action potential (AP). In recent years, optical methods have been developed to record single-SV release (4). Notably, studies using superresolution and total internal reflection fluorescence imaging in functioning central synapses have provided information on the kinetics (5) and subsynaptic localization (6) of single-SV docking and release. Despite these advances, electrophysiological methods remain the most rapid and sensitive method to assess SV exocytosis at central synapses such as the calyx of Held (7) or cerebellar mossy fiber terminals (8). In recent years, electrophysiological recordings performed at special synapses containing a single AZ and a single postsynaptic density (PSD), called "simple synapses," revealed a fixed maximum in the number of SVs that can be released per AZ by a short calcium stimulus (9-11), providing a direct evaluation of the number of docking sites per AZ. This number ran...

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 81%

Numbers of presynaptic Ca ²⁺ channel clusters match those of functionally defined vesicular docking sites in single central synapses

Miki

Kaufmann

Malagón

et al. 2017

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

107

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“…7A). The mature calyx synapse exhibits lower susceptibility to AMPA receptor desensitization (17). During maturation of the calyx of Held, the reduced Ca 2+ influx caused by the shortening of the AP duration is compensated by the tighter spatial coupling of SVs to the calcium source (19,20).…”

Section: Actin Disruption Accelerates Synaptic Depression Of Epscs Evmentioning

confidence: 99%

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

Lee

2012

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

105

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Glutamatergic synaptic terminals harbor reluctant synaptic vesicles (SVs) that contribute little to synchronous release during action potentials but are release competent when stimulated by sucrose or by direct intracellular application of calcium. It has been noted that the proximity of a release-competent SV to the calcium source is one of the primary factors that differentiate reluctant SVs from fastreleasing ones at the calyx of Held synapse. It has not been known whether reluctant SVs can be converted into fast-releasing ones. Here we show that reluctant SVs are recruited rapidly in an actindependent manner to become fast-releasing SVs once the pool of fast-releasing SVs is depleted by a short depolarization. Recovery of the pool of fast-releasing SVs was accompanied by a parallel reduction in the number of reluctant SVs. Quantitative analysis of the time course of depletion of fast-releasing SVs during high-frequency stimulation revealed that in the early phase of stimulation reluctant SVs are converted rapidly into fast-releasing ones, thereby counteracting short-term depression. During the late phase, however, after reluctant vesicles have been used up, another process of calmodulindependent recruitment of fast-releasing SVs is activated. These results document that reluctant SVs have a role in short-term plasticity and support the hypothesis of positional priming, which posits that reluctant vesicles are converted into fast-releasing ones via relocation closer to Ca 2+ -channels.readily releasable pool | synaptic vesicle dynamics S ynaptic strength is determined by quantal size, the number of release-competent synaptic vesicles (SVs), and their release probability (Pr). The estimate for the number of release-competent SVs, which also is referred to as the "readily releasable pool (RRP) size," depends heavily on the method used for its determination. The RRP size estimated by a cumulative plot of the excitatory postsynaptic currents (EPSC) amplitudes evoked by high-frequency afferent fiber stimulation (RRP cum ) is smaller than that estimated by the application of a hypertonic sucrose solution or presynaptic strong depolarization (1-3). This discrepancy reflects the presence of reluctant SVs, which are scarcely released by an action potential (AP) at glutamatergic synaptic terminals. Consistently, deconvolution analysis of EPSCs evoked by a long depolarizing pulse at the calyx of Held revealed that release-competent SVs can be separated into fast-and slowreleasing SV pools (FRP and SRP, respectively) (4). The FRP vesicles are responsible for phasic release during a high-frequency train of action potentials (APs), whereas the SRP vesicles contribute primarily to asynchronous release, when the intracellular concentration of calcium ions ([Ca 2+ ]) is increased globally during the late period of the train (2). Thus, SRP vesicles can be regarded largely as reluctant SVs at the calyx of Held.Despite the evidence for the presence of reluctant SVs at glutamatergic synapses, their role in short-term plasticity i...

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“…2 D). Because the effects of latency fluctuation ("jitter") nearly cancel those of quantal size variability (Taschenberger et al, 2005), correction for quantal variability is not necessary and was therefore not performed.…”

Section: Methodsmentioning

confidence: 99%

Rapid Active Zone Remodeling during Synaptic Plasticity

Weyhersmüller

Hallermann²,

Wagner³

et al. 2011

J. Neurosci.

173

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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Release kinetics, quantal parameters and their modulation during short‐term depression at a developing synapse in the rat CNS

Cited by 108 publications

References 79 publications

Numbers of presynaptic Ca ²⁺ channel clusters match those of functionally defined vesicular docking sites in single central synapses

Numbers of presynaptic Ca ²⁺ channel clusters match those of functionally defined vesicular docking sites in single central synapses

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

Rapid Active Zone Remodeling during Synaptic Plasticity

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Release kinetics, quantal parameters and their modulation during short‐term depression at a developing synapse in the rat CNS

Cited by 108 publications

References 79 publications

Numbers of presynaptic Ca 2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses

Numbers of presynaptic Ca 2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

Rapid Active Zone Remodeling during Synaptic Plasticity

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Product

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Numbers of presynaptic Ca ²⁺ channel clusters match those of functionally defined vesicular docking sites in single central synapses

Numbers of presynaptic Ca ²⁺ channel clusters match those of functionally defined vesicular docking sites in single central synapses