Roles of the Fast-Releasing and the Slowly Releasing Vesicles in Synaptic Transmission at the Calyx of Held

Sakaba, Takeshi

doi:10.1523/jneurosci.0182-06.2006

Cited by 121 publications

(170 citation statements)

References 62 publications

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“…Our results, together with a previous report (2), show that SRP vesicles either can be asynchronously released or can be recruited into the FRP, contributing to the phasic release during HFS. The higher buildup of global [Ca 2+ ] will cause greater asynchronous release of SRP vesicles (33) and thus will reduce the number of SRP vesicles available for SDR.…”

Section: Srp-dependent Recovery Vs Asynchronous Release Of Reluctantsupporting

confidence: 83%

“…The role of reluctantly releasing vesicles in short-term plasticity has not been recognized other than for asynchronous release (2). Based on the finding that these vesicles are very similar in their intrinsic Ca 2+ sensitivity to vesicles contributing to synchronous release (5), positional priming has been proposed as a mechanism for the interconversion between the two types of vesicle (7).…”

Section: Discussionmentioning

confidence: 99%

“…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)(2)(3). This discrepancy reflects the presence of reluctant SVs, which are scarcely released by an action potential (AP) at glutamatergic synaptic terminals.…”

mentioning

confidence: 93%

“…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.…”

mentioning

confidence: 99%

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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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Section: Srp-dependent Recovery Vs Asynchronous Release Of Reluctantsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 93%

mentioning

confidence: 99%

See 2 more Smart Citations

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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“…We therefore asked whether it is obligatory that calmodulin's effect on endocytosis is coupled to its effect on depression. We found stimulation conditions in which calmodulin blockers leave endocytosis untouched but retard the recruitment of fast-releasing synaptic vesicles that are relevant for synchronous release in response to APs at the calyx of Held synapse (12). These results suggest that recruitment of synaptic vesicles does not directly depend on the rate of membrane fission and that it may be regulated by an intermediate step in between exocytosis and membrane fission.…”

mentioning

confidence: 74%

Activity-dependent modulation of endocytosis by calmodulin at a large central synapse

Yao

Sakaba

2011

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

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Although Ca 2+ /calmodulin has been suggested to play a role during endocytosis, it remains unknown if binding of Ca 2+ to calmodulin is essential for initiating endocytosis or if this interaction only has a modulatory effect on endocytosis. In this study, using timeresolved capacitance measurements at the rat calyx of Held synapse, the role of calmodulin in endocytosis was examined. Our results demonstrate that blocking calmodulin with an inhibitory peptide, which interfers with the binding of calmodulin to downstream targets, slowed the rate of endocytosis, but only when accompanied by high Ca 2+ influx. In response to a short train of action potential-like stimulation, blocking calmodulin had no effect on endocytosis. Furthermore, we have identified conditions in which inhibition of calmodulin fails to affect the rate of endocytosis, but nevertheless retards recruitment of synaptic vesicles to the fast-releasing vesicle pool responsible for synchronous release. The results indicate that calmodulin facilitates endocytosis in an activity-dependent manner but is not mandatory for endocytosis, and suggest that calmodulin modulates an endocytotic intermediate process, which in turn affects synaptic vesicle recruitment and membrane fission.protein kinase A | synaptic transmission | calcium A t the presynaptic terminal, the role of Ca 2+ in endocytosis remains unclear. Depending on the preparation, Ca 2+ either accelerates the rate of endocytosis, has no apparent effects (1), or can inhibit (2). In addition, it is unknown whether the increase in intraterminal [Ca 2+ ] initiates endocytosis in an all-ornone manner or has only a modulatory role. The uncertainty may partially arise from the different kinetic components of endocytosis that have been observed both within a given cell type and among different preparations (3, 4).The calyx of Held synapse has a large presynaptic terminal where direct recordings can be performed (5). In this preparation, presynaptic capacitance measurements allow for the monitoring of membrane retrieval with high temporal resolution (6). At the calyx synapse, it has recently been shown that both rapid and slow forms of endocytosis are Ca 2+ -dependent and are sensitive to calmodulin inhibitors (7). Based on these results, it was subsequently postulated that Ca 2+ /calmodulin is the major Ca 2+ sensor for endocytosis. However, the stimulation protocols used in this previous study were not representative of physiological conditions. Thus, it remains unclear whether calmodulin triggers endocytosis in response to milder, more physiologically relevant stimulation. Finally, although Wu et al. (7) concluded that Ca 2+ /calmodulin is the major sensor for endocytosis, recent studies have demonstrated that other Ca 2+ sensors can mediate various forms of endocytosis in this (8, but see ref. 7) and other preparations (9).Because of the unanswered questions surrounding the role of calmodulin and other Ca 2+ sensors during endocytosis, we applied more physiologically relevant stimulation to the calyx o...

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Slow‐decaying presynaptic calcium dynamics gate long‐lasting asynchronous release at the hippocampal mossy fiber to CA3 pyramidal cell synapse

Chamberland

Timofeeva

Evstratova

et al. 2020

Synapse

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Neurotransmitter release from presynaptic terminals occurs in different modes following action potential firing. Action potentials propagating along the axon reach the presynaptic terminal and generate Ca 2+ influx, which causes vesicle fusion and neurotransmitter release. Synchronous and asynchronous release both depend on a common presynaptic Ca 2+ influx, but with different dependency on the Ca 2+ concentration (Atluri

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Roles of the Fast-Releasing and the Slowly Releasing Vesicles in Synaptic Transmission at the Calyx of Held

Cited by 121 publications

References 62 publications

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

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

Activity-dependent modulation of endocytosis by calmodulin at a large central synapse

Slow‐decaying presynaptic calcium dynamics gate long‐lasting asynchronous release at the hippocampal mossy fiber to CA3 pyramidal cell synapse

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