New and Corrected Simulations of Synaptic Facilitation

Matveev, Victor; Sherman, Arthur; Zucker, Robert S.

doi:10.1016/s0006-3495(02)73907-6

Cited by 86 publications

(101 citation statements)

References 14 publications

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“…A similar conclusion was reached based on a different model (Matveev et al 2006) also with four Ca 2ϩ binding sites (2 with high and 2 with low unbinding rates). A series of computational studies on the crayfish NMJ using a finite-difference method (Matveev et al 2002;Tang et al 2000) and on the amphibian NMJ via a Monte Carlo approach (Bennett et al 2004) also used four Ca 2ϩ binding sites (3 with high and 1 with low unbinding rates). In the latter study the two types of Ca 2ϩ binding sites were segregated in space (Ͼ150 nm) to avoid saturation of the high-affinity binding site.…”

Section: Discussionmentioning

confidence: 99%

New insights into short-term synaptic facilitation at the frog neuromuscular junction

Kelly

Ingram

et al. 2015

Journal of Neurophysiology

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Short-term synaptic facilitation occurs during high-frequency stimulation, is known to be dependent on presynaptic calcium ions, and persists for tens of milliseconds after a presynaptic action potential. We have used the frog neuromuscular junction as a model synapse for both experimental and computer simulation studies aimed at testing various mechanistic hypotheses proposed to underlie short-term synaptic facilitation. Building off our recently reported excess-calcium-binding-site model of synaptic vesicle release at the frog neuromuscular junction (Dittrich M, Pattillo JM, King JD, Cho S, Stiles JR, Meriney SD. Biophys J 104: 2751–2763, 2013), we have investigated several mechanisms of short-term facilitation at the frog neuromuscular junction. Our studies place constraints on previously proposed facilitation mechanisms and conclude that the presence of a second class of calcium sensor proteins distinct from synaptotagmin can explain known properties of facilitation observed at the frog neuromuscular junction. We were further able to identify a novel facilitation mechanism, which relied on the persistent binding of calcium-bound synaptotagmin molecules to lipids of the presynaptic membrane. In a real physiological context, both mechanisms identified in our study (and perhaps others) may act simultaneously to cause the experimentally observed facilitation. In summary, using a combination of computer simulations and physiological recordings, we have developed a stochastic computer model of synaptic transmission at the frog neuromuscular junction, which sheds light on the facilitation mechanisms in this model synapse.

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Section: Discussionmentioning

confidence: 99%

New insights into short-term synaptic facilitation at the frog neuromuscular junction

Kelly

Ingram

et al. 2015

Journal of Neurophysiology

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“…7D), suggesting an additional faster depression (Dobrunz et al, 1997;Varela et al, 1997), or that factors in addition to depletion may be contributing to depression (Zucker and Regehr, 2002). A third approach that will be important to quantify dynamic changes in the components is modeling of the release process Sen et al, 1996;Varela et al, 1997;Dittman et al, 2000;Matveev et al, 2002;Aristizabal and Glavinovic, 2003).…”

Section: Discussionmentioning

confidence: 99%

Augmentation Increases Vesicular Release Probability in the Presence of Masking Depression at the Frog Neuromuscular Junction

Kalkstein

Magleby

2004

J. Neurosci.

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Synaptic augmentation is a short-term component of synaptic plasticity that increases transmitter release during repetitive stimulation and decays thereafter with a time constant of ϳ7 sec. Augmentation has typically been observed under conditions where there is little or no depression because of depletion of synaptic vesicles from the readily releasable pool (RRP) of transmitter. We now study augmentation under conditions of pronounced depression at the frog neuromuscular junction to gain additional insight into mechanism. If augmentation reflects an increase in the size of the RRP of transmitter, then augmentation should not be present with depression. Our findings using four different experimental approaches suggested that augmentation was still present in the presence of pronounced depression: mathematical extraction of augmentation from the changes in transmitter release after repetitive stimulation, identification of augmentation with Ba 2ϩ , correction of the data for the measured depletion of the RRP, and identification of an augmentation component of residual Ca 2ϩ . We conclude that the augmentation machinery still acts to increase transmitter release when depression reduces the RRP sufficiently to mask obvious augmentation. The masked augmentation was found to increase transmitter release by increasing the probability of releasing individual vesicles from the depressed RRP, countering the effects of depression. Because augmentation and depression have similar time courses, either process can mask the other, depending on their relative magnitudes. Consequently, the apparent absence of one of the processes does not exclude that it is still contributing to short-term synaptic plasticity.

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“…The resulting Ca(t) was almost exactly described by a Gaussian curve, so a closely fitting Gaussian curve ( ϭ 250 s) was used to represent Ca(t). The peak [Ca 2ϩ ] i amplitude reached during an action potential depends critically on the Ca 2ϩ flux per channel, the number of Ca 2ϩ channels opening near a docked vesicle, their exact distances from the secretory trigger, and the binding kinetics and mobilities of endogenous buffers (Tang et al, 2000;Matveev et al, 2002Matveev et al, , 2004. Because none of these is known with sufficient precision, the peak [Ca 2ϩ ] i amplitude produced by an action potential at the secretory trigger remained a free parameter (cf.…”

Section: Methodsmentioning

confidence: 99%

Calcium Sensitivity of Neurotransmitter Release Differs at Phasic and Tonic Synapses

Millar¹,

Zucker²,

Ellis‐Davies³

et al. 2005

J. Neurosci.

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The efficacy of synaptic transmission varies greatly among synaptic contacts. We have explored the origins of differences between phasic and tonic crustacean neuromuscular junctions. Synaptic boutons of a phasic motor neuron release three orders of magnitude more quanta to a single action potential and show strong depression to a train, whereas tonic synapses are nearly unresponsive to single action potentials and display an immense facilitation.

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New and Corrected Simulations of Synaptic Facilitation

Cited by 86 publications

References 14 publications

New insights into short-term synaptic facilitation at the frog neuromuscular junction

New insights into short-term synaptic facilitation at the frog neuromuscular junction

Augmentation Increases Vesicular Release Probability in the Presence of Masking Depression at the Frog Neuromuscular Junction

Calcium Sensitivity of Neurotransmitter Release Differs at Phasic and Tonic Synapses

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