Competition between Phasic and Asynchronous Release for Recovered Synaptic Vesicles at Developing Hippocampal Autaptic Synapses

Otsu, Yo; Shahrezaei, Vahid; Li, Bo; Raymond, Lynn A.; Delaney, Kerry R.; Murphy, Timothy H.

doi:10.1523/jneurosci.4452-03.2004

Cited by 147 publications

(233 citation statements)

References 78 publications

(130 reference statements)

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“…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. This idea is consistent with the previous finding that asynchronous release and phasic release compete for a common, limited supply of release-competent SVs (34). Therefore, the fate of SRP vesicles-conversion to FRP vesicles or asynchronous release-may be determined by presynaptic global [Ca 2+ ] i .…”

Section: Srp-dependent Recovery Vs Asynchronous Release Of Reluctantsupporting

confidence: 92%

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: 92%

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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“…Under the working hypothesis of vesicle maturation, it is also expected that synchronous release remains depressed as long as the slowly releasing vesicle pool is not refilled. In this respect, it is possible that ongoing asynchronous release causes further depression of the synchronous release component, as has been shown by Otsu et al (2004). It is also possible that asynchronous release can access both immediately and readily releasable pools of synaptic vesicles, depending on the stimulation patterns, regulation of Ca 2ϩ buffering, and extrusion in the presynaptic terminal as proposed by Hagler and Goda (2001).…”

Section: Discussionmentioning

confidence: 85%

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

Sakaba¹

2006

J. Neurosci.

122

150

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In the calyx of Held, fast and slow components of neurotransmitter release can be distinguished during a step depolarization. The two components show different sensitivity to molecular/pharmacological manipulations. Here, their roles during a high-frequency train of action potential (AP)-like stimuli were examined by using both deconvolution of EPSCs and presynaptic capacitance measurements. During a 100 Hz train of AP-like stimuli, synchronous release showed a pronounced depression within the 20 stimuli. Asynchronous release persisted during the train, was variable in its amount, and was more prominent during a 300 Hz train. We have shown previously that slowly releasing vesicles were recruited faster than fast-releasing vesicles after depletion. By further slowing recovery of the fastreleasing vesicles by inhibiting calmodulin-dependent processes (Sakaba and Neher, 2001b), the slowly releasing vesicles were isolated during recovery from vesicle depletion. When a high-frequency train was applied, the isolated slowly releasing vesicles were released predominantly asynchronously. In contrast, synchronous release was mediated mainly by the fast-releasing vesicles. The results suggest that fast-releasing vesicles contribute mainly to synchronous release and that depletion of fast-releasing vesicles shape the synaptic depression of the synchronous phase of EPSCs, whereas slowly releasing vesicles are released mainly asynchronously during highfrequency stimulation. The latter is less subject to depression presumably because of a rapid vesicular recruitment process, which is a characteristic of this component.

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“…Ca 2+ entry through Ca V 2 channels triggers the fusion of synaptic vesicles, initiating synaptic transmission that occurs in two phases: a fast synchronous component and a slower asynchronous component that builds during trains of action potentials. The fraction of synaptic vesicle exocytosis that is mediated by the slower asynchronous release process varies from synapse to synapse (38)(39)(40)(41)(42)(43)(44). In some synapses, asynchronous neurotransmitter release can exceed …”

Section: Resultsmentioning

confidence: 99%

Asynchronous Ca ² ⁺ current conducted by voltage-gated Ca ²⁺ (Ca _V )-2.1 and Ca _V 2.2 channels and its implications for asynchronous neurotransmitter release

Few¹,

Nanou²,

Watari

et al. 2012

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

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We have identified an asynchronously activated Ca 2+ current through voltage-gated Ca 2+ (Ca V )-2.1 and Ca V 2.2 channels, which conduct P/Qand N-type Ca 2+ currents that initiate neurotransmitter release. In nonneuronal cells expressing Ca V 2.1 or Ca V 2.2 channels and in hippocampal neurons, prolonged Ca 2+ entry activates a Ca 2+ current, I Async , which is observed on repolarization and decays slowly with a halftime of 150-300 ms. I Async is not observed after L-type Ca 2+ currents of similar size conducted by Ca V 1.2 channels. I Async is Ca 2+ -selective, and it is unaffected by changes in Na + , K + , Cl − , or H + or by inhibitors of a broad range of ion channels. During trains of repetitive depolarizations, I Async increases in a pulse-wise manner, providing Ca 2+ entry that persists between depolarizations. In single-cultured hippocampal neurons, trains of depolarizations evoke excitatory postsynaptic currents that show facilitation followed by depression accompanied by asynchronous postsynaptic currents that increase steadily during the train in parallel with I Async . I Async is much larger for slowly inactivating Ca V 2.1 channels containing β 2a -subunits than for rapidly inactivating channels containing β 1b -subunits. I Async requires global rises in intracellular Ca 2+ , because it is blocked when Ca 2+ is chelated by 10 mM EGTA in the patch pipette. Neither mutations that prevent Ca 2+ binding to calmodulin nor mutations that prevent calmodulin regulation of Ca V 2.1 block I Async . The rise of I Async during trains of stimuli, its decay after repolarization, its dependence on global increases of Ca 2+ , and its enhancement by β 2a -subunits all resemble asynchronous release, suggesting that I Async is a Ca 2+ source for asynchronous neurotransmission.asynchronous synaptic transmission | exocytosis V oltage-gated Ca 2+ (Ca V ) channels are activated by depolarization and conduct inward Ca 2+ currents that initiate many cellular responses to electrical signaling (1). Ca V 2 channels conduct P/Q-, N-, and R-type currents in presynaptic nerve terminals, and Ca 2+ entry through these channels initiates neurotransmitter release at conventional synapses (1-3). P/Q-and N-type Ca 2+ currents conducted by Ca V 2.1 and Ca V 2.2 channels, respectively, are more efficiently coupled to neurotransmitter release than Rtype Ca 2+ currents conducted by Ca V 2.3 channels (4, 5). Neurotransmitter release occurs in two phases: a fast synchronous (phasic) component and a slow asynchronous (tonic) component (6). The slower asynchronous component of release is proposed to result from residual Ca 2+ remaining after an action potential acting on a different Ca 2+ sensor than the sensor for synchronous neurotransmitter release (6-8). Remarkably, when synchronous release is prevented by deletion of its Ca 2+ sensor synaptotagmin, the asynchronous release process can cause exocytosis of the entire readily releasable pool, suggesting a functional competition between synchronous and asynchronous release processes for the ...

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Competition between Phasic and Asynchronous Release for Recovered Synaptic Vesicles at Developing Hippocampal Autaptic Synapses

Cited by 147 publications

References 78 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

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

Asynchronous Ca ² ⁺ current conducted by voltage-gated Ca ²⁺ (Ca _V )-2.1 and Ca _V 2.2 channels and its implications for asynchronous neurotransmitter release

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Competition between Phasic and Asynchronous Release for Recovered Synaptic Vesicles at Developing Hippocampal Autaptic Synapses

Cited by 147 publications

References 78 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

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

Asynchronous Ca 2 + current conducted by voltage-gated Ca 2+ (Ca V )-2.1 and Ca V 2.2 channels and its implications for asynchronous neurotransmitter release

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Asynchronous Ca ² ⁺ current conducted by voltage-gated Ca ²⁺ (Ca _V )-2.1 and Ca _V 2.2 channels and its implications for asynchronous neurotransmitter release