Inhibitory Transmission Mediated by Asynchronous Transmitter Release

Lu, Tao; Trussell, Laurence O.

doi:10.1016/s0896-6273(00)81204-0

Cited by 208 publications

(244 citation statements)

References 66 publications

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“…In this case, the asynchronous release rate could be an upper limit of the recovery rate. A similar phenomenon was postulated for GABAergic synapses onto avian nucleus magnocellularis neurons (Lu and Trussell, 2000). Moreover, because a prolonged decay of asynchronous release is associated with slower phasic release recovery, it is possible that the two modes of release compete for the same pool of vesicles.…”

Section: A Common Pool Model For Phasic and Asynchronous Releasesupporting

confidence: 63%

“…Here, we set out to examine how asynchronous release can still proceed despite depression of phasic release during repetitive stimulation. One possibility is that asynchronous release may not necessarily be dependent on a store of readily releasable quanta, but rather depend on the process by which quanta are rapidly refilled into the store and subjected to immediate release (Lu and Trussell, 2000). Assuming the depression of evoked release is attributed to the depletion of readily releasable pools (RRPs) of vesicles (Elmqvist and Quastel, 1965;Rosenmund and Stevens, 1996;Dobrunz and Stevens, 1997), the maximum rate of asynchronous release would approximate to the upper limit for the refilling rate of the RRP.…”

Section: Introductionmentioning

confidence: 99%

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

Otsu¹,

Shahrezaei²,

Li³

et al. 2004

J. Neurosci.

147

189

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Developing hippocampal neurons in microisland culture undergo rapid and extensive transmitter release-dependent depression of evoked (phasic) excitatory synaptic activity in response to 1 sec trains of 20 Hz stimulation. Although evoked phasic release was attenuated by repeated stimuli, asynchronous (miniature like) release continued at a high rate equivalent to ϳ2.8 readily releasable pools (RRPs) of quanta/sec. Asynchronous release reflected the recovery and immediate release of quanta because it was resistant to sucroseinduced depletion of the RRP. Asynchronous and phasic release appeared to compete for a common limited supply of release-ready quanta because agents that block asynchronous release, such as EGTA-AM, led to enhanced steady-state phasic release, whereas prolongation of the asynchronous release time course by LiCl delayed recovery of phasic release from depression. Modeling suggested that the resistance of asynchronous release to depression was associated with its ability to out-compete phasic release for recovered quanta attributable to its relatively low release rate (up to 0.04/msec per vesicle) stimulated by bulk intracellular Ca 2ϩ concentration ([ Ca 2ϩ ] i ) that could function over prolonged intervals between successive stimuli. Although phasic release was associated with a considerably higher peak rate of release (0.4/msec per vesicle), the [Ca 2ϩ ] i microdomains that trigger it are brief (1 msec), and with asynchronous release present, relatively few quanta can accumulate within the RRP to be available for phasic release. We conclude that despite depression of phasic release during train stimulation, transmission can be maintained at a near-maximal rate by switching to an asynchronous mode that takes advantage of a bulk presynaptic [Ca 2ϩ ] i .

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Section: A Common Pool Model For Phasic and Asynchronous Releasesupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

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

Otsu¹,

Shahrezaei²,

Li³

et al. 2004

J. Neurosci.

147

189

View full text Add to dashboard Cite

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“…The approach shown here is limited to a few preparations, in which vesicle pools can be directly measured, but it may be helpful for the formulation of reasonable models in small synapses, which are not accessible by conventional methods. Specifically, the observation here may have an implication for the synapses where asynchronous release is copious and increases during a high-frequency stimulation (Vincient and Marty, 1996;Lu and Trussell, 2000;Hefft and Jonas, 2005). Although this may be explained by differences in regulation of presynaptic Ca 2ϩ concentration and Ca 2ϩ sensitivity of transmitter release (Millar et al, 2005), an alternative explanation could be that the ratio of the fast-releasing and the slowly releasing vesicles differs among synapses.…”

Section: Discussionmentioning

confidence: 75%

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

Sakaba¹

2006

J. Neurosci.

121

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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Inhibitory Transmission Mediated by Asynchronous Transmitter Release

Cited by 208 publications

References 66 publications

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

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

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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Inhibitory Transmission Mediated by Asynchronous Transmitter Release

Cited by 208 publications

References 66 publications

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

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

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