Quantitative Analysis of Calcium-Dependent Vesicle Recruitment and Its Functional Role at the Calyx of Held Synapse

Hosoi, Nobutake; Sakaba, Takeshi; Neher, Erwin

doi:10.1523/jneurosci.4122-07.2007

Cited by 130 publications

(155 citation statements)

References 71 publications

(135 reference statements)

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“…1C). In agreement with previous reports (6,16), latrunculin B (15 μM; n = 7) inhibited CDR and SDR, and CaMip (20 μM; n = 7) abolished CDR ( Fig. 1D).…”

Section: Resultssupporting

confidence: 93%

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Superpriming of synaptic vesicles after their recruitment to the readily releasable pool

Lee

Neher

et al. 2013

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

103

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Recruitment of release-competent vesicles during sustained synaptic activity is one of the major factors governing short-term plasticity. During bursts of synaptic activity, vesicles are recruited to a fast-releasing pool from a reluctant vesicle pool through an actin-dependent mechanism. We now show that newly recruited vesicles in the fast-releasing pool do not respond at full speed to a strong Ca 2+ stimulus, but require approximately 4 s to mature to a "superprimed" state. Superpriming was found to be altered by agents that modulate the function of unc13 homolog proteins (Munc13s), but not by calmodulin inhibitors or actin-disrupting agents. These findings indicate that recruitment and superpriming of vesicles are regulated by separate mechanisms, which require integrity of the cytoskeleton and activation of Munc13s, respectively. We propose that refilling of the fast-releasing vesicle pool proceeds in two steps, rapid actin-dependent "positional priming," which brings vesicles closer to Ca 2+ sources, followed by slower superpriming, which enhances the Ca 2+ sensitivity of primed vesicles.T he release rate of a synaptic vesicle (SV) is governed by two factors, the intrinsic Ca 2+ sensitivity of the vesicle fusion machinery and the distance of the SV to Ca 2+ channels. As Munc13s and Munc18s confer fusion competence on a docked SV, the regulation of release rate by Munc13s and Munc18s is called "molecular priming" (1). It is distinguished from "positional priming," a process that is thought to regulate the proximity of an SV to the calcium source (2, 3). However, it is not known how these two priming mechanisms are manifested in the kinetics of quantal release. Deconvolution analyses of excitatory postsynaptic currents (EPSCs) evoked by long presynaptic depolarizations at the calyx of Held (a giant nerve terminal in the auditory pathway) showed that releasable SVs can be separated into fastreleasing pools (FRPs) and slowly releasing pools (SRPs) (4). The differences in SV priming that underlie the differences in release kinetics between SVs in the FRP and the SRP are currently unclear (3, 5). Wadel et al. (3) found that SVs in the SRP can be released by homogenous Ca 2+ elevation only 1.5 to 2 times slower than SVs in the FRP, even though they are released 10 times slower by depolarization-induced Ca 2+ influx. This was interpreted as evidence that the differences in their release kinetics arise from differences primarily in positional priming. In contrast, Wölfel et al. (5) showed that release with two kinetic components is even observed if the intracellular Ca 2+ concentration is homogenously elevated throughout the calyx terminal, indicating that SVs in the FRP and the SRP differ with regard to their molecular priming.We found recently that SVs in the SRP rapidly convert into the FRP after specific FRP depletion by a short depolarizing pulse (6). Such rapid refilling of the FRP with SRP vesicles, which is referred to as SRP-dependent recovery (SDR), was suppressed by actin depolymerization or inhibition ...

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“…1C). In agreement with previous reports (6,16), latrunculin B (15 μM; n = 7) inhibited CDR and SDR, and CaMip (20 μM; n = 7) abolished CDR ( Fig. 1D).…”

Section: Resultssupporting

confidence: 93%

“…CaM inhibitors specifically affect CDR (6,16) and have little effect on SDR and the recovery of τ fast (Fig. 2B).…”

Section: Discussionmentioning

confidence: 93%

Superpriming of synaptic vesicles after their recruitment to the readily releasable pool

Lee

Neher

et al. 2013

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

103

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“…However, elevations of presynaptic calcium can greatly accelerate recovery from depression (Dittman and Regehr 1998;Wesseling 1998, 1999;Wang and Kaczmarek 1998;Sakaba 2008;Yang and Xu-Friedman 2008), presumably by accelerating replenishment of the RRP. This acceleration is prevented by inhibiting calmodulin Hosoi et al 2007), but the downstream target of calmodulin remains unclear. Munc13 is a potential target of calmodulin that is involved in priming vesicles (Augustin et al 1999).…”

Section: Calcium-dependent Recovery From Depressionmentioning

confidence: 99%

“…Munc13 is a potential target of calmodulin that is involved in priming vesicles (Augustin et al 1999). Replenishment of release-ready vesicles is approximately linearly related to presynaptic calcium levels, and during high-frequency stimulus trains calcium can accelerate vesicle recruitment by a factor of 10 (Hosoi et al 2007). …”

Section: Calcium-dependent Recovery From Depressionmentioning

confidence: 99%

Short-Term Presynaptic Plasticity

Regehr

2012

Cold Spring Harbor Perspectives in Biology

425

358

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“…According to these hypotheses, facilitation is caused by the accumulation of residual calcium in the presynaptic bouton, while depression is due to the depletion of the neurotransmitter vesicle pool. Additionally, the recovery of the depleted vesicle pool has been shown to be dependent on the residual calcium concentration (Dittman and Regehr 1998;Wang and Kaczmarek 1998;Hosoi et al 2007). Depletion-independent mechanisms of depression were also reported (Hsu et al 1996;Kraushaar and Jonas 2000;Waldeck et al 2000;Gover et al 2002;Kirischuk et al 2002;Pedroarena and Schwarz 2003;Fuhrmann et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Parametric and non-parametric modeling of short-term synaptic plasticity. Part I: computational study

2008

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Parametric and non-parametric modeling methods are combined to study the short-term plasticity (STP) of synapses in the central nervous system (CNS). The nonlinear dynamics of STP are modeled by means: (1) previously proposed parametric models based on mechanistic hypotheses and/or specific dynamical processes, and (2) non-parametric models (in the form of Volterra kernels) that transforms the presynaptic signals into postsynaptic signals. In order to synergistically use the two approaches, we estimate the Volterra kernels of the parametric models of STP for four types of synapses using synthetic broadband input-output data. Results show that the non-parametric models accurately and efficiently replicate the input-output transformations of the parametric models. Volterra kernels provide a general and quantitative representation of the STP.

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Quantitative Analysis of Calcium-Dependent Vesicle Recruitment and Its Functional Role at the Calyx of Held Synapse

Cited by 130 publications

References 71 publications

Superpriming of synaptic vesicles after their recruitment to the readily releasable pool

Superpriming of synaptic vesicles after their recruitment to the readily releasable pool

Short-Term Presynaptic Plasticity

Parametric and non-parametric modeling of short-term synaptic plasticity. Part I: computational study

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