Developmental regulation of the intracellular Ca<sup>2+</sup> sensitivity of vesicle fusion and Ca<sup>2+</sup>–secretion coupling at the rat calyx of Held

Kochubey, Olexiy; Han, Yunyun; Schneggenburger, Ralf

doi:10.1113/jphysiol.2009.172387

Cited by 67 publications

(117 citation statements)

References 53 publications

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“…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). It is puzzling, however, that the mature calyx of Held still harbors a large number of SRP vesicles (20,21). To test whether SRP vesicles are recruited to the phasic release, we examined the effect of latB at the mature calyx synapse in the presence of 2 mM γ-DGG.…”

Section: Actin Disruption Accelerates Synaptic Depression Of Epscs Evmentioning

confidence: 98%

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: Actin Disruption Accelerates Synaptic Depression Of Epscs Evmentioning

confidence: 98%

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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“…6C). The large majority of the cumulative release traces required doubleexponential fits, indicating that Ca 2ϩ uncaging evoked both a fast and a slow release component (Wölfel et al, 2007;Kochubey et al, 2009). Following 20 Hz stimulation, the amplitude of the fast release component, which reflects release from the FRP, was significantly reduced from 1669 Ϯ 103 vesicles under control conditions to 652 Ϯ 82 vesicles following the 20 Hz train (n ϭ 17 cell pairs with Ca 2ϩ uncaging; p Ͻ 0.001).…”

Section: Intrinsically Decreased Release Kinetics Of Vesicles Remainimentioning

confidence: 99%

“…6 D), Ca 2ϩ -dependent transmitter release was modeled by an allosteric model of Ca 2ϩ binding and vesicle fusion . We assumed a single pool of fast-releasable vesicles (1500 vesicles) and drove the model with the previously calculated [Ca 2ϩ ] i waveform expected for the fast flash lamp (Kochubey et al, 2009) …”

Section: Methodsmentioning

confidence: 99%

Interaction between Facilitation and Depression at a Large CNS Synapse Reveals Mechanisms of Short-Term Plasticity

Müller

Goutman²,

Kochubey³

et al. 2010

J. Neurosci.

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The two fundamental forms of short-term plasticity, short-term depression and facilitation, coexist at most synapses, but little is known about their interaction. Here, we studied the interplay between short-term depression and facilitation at calyx of Held synapses. Stimulation at a "low" frequency of 10 or 20 Hz, which is in the range of the spontaneous activity of these auditory neurons in vivo, induced synaptic depression. Surprisingly, an instantaneous increase of the stimulation frequency to 100 or 200 Hz following the low-frequency train uncovered a robust facilitation of EPSCs relative to the predepressed amplitude level. This facilitation decayed rapidly (ϳ30 ms) and depended on presynaptic residual Ca 2ϩ , but it was not caused by Ca 2ϩ current facilitation. To probe the release probability of the remaining readily releasable vesicles following the low-frequency train we made presynaptic Ca 2ϩ uncaging experiments in the predepressed state of the synapse. We found that low-frequency stimulation depletes the fast-releasable vesicle pool (FRP) down to ϳ40% of control and that the remaining FRP vesicles are released with ϳ2-fold slower release kinetics, indicating a hitherto unknown intrinsic heterogeneity among FRP vesicles. Thus, vesicles with an intrinsically lower release probability predominate after low frequency stimulation and undergo facilitation during the onset of subsequent high-frequency trains. Facilitation in the predepressed state of the synapse might help to stabilize the amount of transmitter release at the onset of high-frequency firing at these auditory synapses.

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“…In hearing animals, STD was not observed anymore (Lorteije et al, 2009) and, also, transmission failures were rare, suggesting that STD is of little relevance in hearing animals, at least during spontaneous activity. The underlying physiological conditions are the adult-like size of readily releasable vesicle pools, a sufficient exocytosis efficiency, and the reduced release probability compensated by tighter coupling of vesicles to calcium channels (Taschenberger and von Gersdorff, 2000;Futai et al, 2001;Iwasaki and Takahashi, 2001;Joshi and Wang, 2002;Taschenberger et al, 2002;Fedchyshyn and Wang, 2005;Yang and Wang, 2006;Wang et al, 2008;Kochubey et al, 2009;Leão and von Gersdorff, 2009). The transmission delay and the amplitude of the postsynaptic AP also underlie strong activity-dependent plasticity in prehearing mice and, to a lesser extent, also in hearing animals.…”

Section: Development Of Activity-dependent Plasticitymentioning

confidence: 99%

The Calyx of Held Develops Adult-Like Dynamics and Reliability by Hearing Onset in the MouseIn Vivo

Sonntag¹,

Englitz²,

Typlt³

et al. 2011

J. Neurosci.

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The development of the auditory system has received increasing attention since the mechanisms of patterned, spontaneous activity in prehearing mammals were discovered. This early activity originates in the cochlea and is assumed to be of importance for the establishment and refinement of synaptic connections in the auditory system. In the present study we investigate synaptic transmission and its interplay with spontaneous discharges in the developing auditory system. We used the calyx of Held as a model system, where this question can be investigated in vivo over a broad range of ages [postnatal day 8 (P8)-P28]. To precisely quantify the timing and reliability of synaptic transmission, we developed a novel fitting approach which decomposes the extracellularly recorded signal into its presynaptic and postsynaptic components. In prehearing mice, we found signal transmission to be unreliable, with high variability in the transmission delay and in the amplitude of postsynaptic components. These timing and amplitude changes were strongly correlated with the preceding activity. Around hearing onset (P12-P14), the properties of signal transmission converged to the adult-like state which was characterized by high transmission reliability as well as high consistency in timing and amplitude. Although activity-dependent depression was still found in action potentials, EPSP depression no longer played a prominent role. In conclusion, the maturation of synaptic transmission at the calyx of Held seems to be precisely timed to achieve its adult potential by the time acoustically evoked signal processing commences.

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Developmental regulation of the intracellular Ca²⁺ sensitivity of vesicle fusion and Ca²⁺–secretion coupling at the rat calyx of Held

Cited by 67 publications

References 53 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

Interaction between Facilitation and Depression at a Large CNS Synapse Reveals Mechanisms of Short-Term Plasticity

The Calyx of Held Develops Adult-Like Dynamics and Reliability by Hearing Onset in the MouseIn Vivo

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Developmental regulation of the intracellular Ca2+ sensitivity of vesicle fusion and Ca2+–secretion coupling at the rat calyx of Held

Cited by 67 publications

References 53 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

Interaction between Facilitation and Depression at a Large CNS Synapse Reveals Mechanisms of Short-Term Plasticity

The Calyx of Held Develops Adult-Like Dynamics and Reliability by Hearing Onset in the MouseIn Vivo

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Developmental regulation of the intracellular Ca²⁺ sensitivity of vesicle fusion and Ca²⁺–secretion coupling at the rat calyx of Held