Synaptic Vesicle Mobility in Mouse Motor Nerve Terminals with and without Synapsin

Gaffield, Michael A.; Betz, William J.

doi:10.1523/jneurosci.3910-07.2007

Cited by 82 publications

(96 citation statements)

References 57 publications

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“…However, the mobility of synaptic vesicles was not altered in the knock-outs (Gaffield and Betz, 2007), and both the putative immobile reserve and recycling reserve pools (Rizzoli and Betz, 2005) were decreased by similar amounts (Pieribone et al, 1995;Rosahl et al, 1995;Bogen et al, 2006), contrary to the expectation that only one of the two pools would be affected. In addition, our own attempts to incorporate into kinetic models the idea that synapsin phosphorylation accelerates vesicle trafficking have not been successful because the idea ultimately invokes mass-action rules to explain the speed of vesicle trafficking.…”

Section: Synapsin Hypothesiscontrasting

confidence: 57%

A New Kinetic Framework for Synaptic Vesicle Trafficking Tested in Synapsin Knock-Outs

Gabriel¹,

García‐Pérez²,

Mahfooz³

et al. 2011

J. Neurosci.

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At least two rate-limiting mechanisms in vesicle trafficking operate at mouse Schaffer collateral synapses, but their molecular/physical identities are unknown. The first mechanism determines the baseline rate at which reserve vesicles are supplied to a readily releasable pool. The second causes the supply rate to depress threefold when synaptic transmission is driven hard for extended periods. Previous models invoked depletion of a reserve vesicle pool to explain the reductions in the supply rate, but the mass-action assumption at their core is not compatible with kinetic measurements of neurotransmission under maximal-use conditions. Here we develop a new theoretical model of rate-limiting steps in vesicle trafficking that is compatible with previous and new measurements. A physical interpretation is proposed where local reserve pools consisting of four vesicles are tethered to individual release sites and are replenished stochastically in an all-or-none fashion. We then show that the supply rate depresses more rapidly in synapsin knock-outs and that the phenotype can be fully explained by changing the value of the single parameter in the model that would specify the size of the local reserve pools. Vesicle-trafficking rates between pools were not affected. Finally, optical imaging experiments argue against alternative interpretations of the theoretical model where vesicle trafficking is inhibited without reserve pool depletion. This new conceptual framework will be useful for distinguishing which of the multiple molecular and cell biological mechanisms involved in vesicle trafficking are rate limiting at different levels of synaptic throughput and are thus candidates for physiological and pharmacological modulation.

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Section: Synapsin Hypothesiscontrasting

confidence: 57%

A New Kinetic Framework for Synaptic Vesicle Trafficking Tested in Synapsin Knock-Outs

Gabriel¹,

García‐Pérez²,

Mahfooz³

et al. 2011

J. Neurosci.

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“…Disruption of actin in frog motor nerve terminals showed no significant changes in vesicular mobility (Gaffield et al 2006). In knockout mice lacking synapsins, the neurons display no gross anatomical abnormalities (Rosahl et al 1995) or changes in synaptic vesicle trafficking (Gaffield and Betz 2007). In rat ribbon synapses (unique neurons that have a high rate of neurotransmitter release), there is an absence of synapsin, suggesting that vesicle clustering and mobilization involves a different process (Mandell et al 1990).…”

Section: Discussionmentioning

confidence: 99%

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Bui

Glavinović

2012

Cogn Neurodyn

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Short-term synaptic depression mainly reflects the depletion of the readily releasable pool (RRP) of quanta. Its dynamics, and especially the replenishment rate of the RRP, are still not well characterized in spite of decades of investigation. Main reason is that the vesicular storage and release system is treated as time-independent. If it is time-dependent all parameters thus estimated become problematic. Indeed the reports about how prolonged stimulation affects the dynamics are contradictory. To study this, we used patterned stimulation on the Schaeffer collateral fiber pathway and model-fitting of the excitatory post-synaptic currents (EPSC) recorded from CA1 neurons in rat hippocampal slices. The parameters of a vesicular storage and release model with two pools were estimated by minimizing the squared difference between the ESPC amplitudes and simulated model output. This yields the 'basic' parameters (release coupling, replenishment coupling and RRP size) that underlie the 'derived' and commonly used parameters (fractional release and replenishment rate). The fractional release increases when [Ca ?? ] o is raised, whereas the replenishment rate is [Ca ?? ] o independent. Fractional release rises because release coupling increases, and the RRP becomes less able to contain quanta. During prolonged stimulation, the fractional release remains generally unaltered, whereas the replenishment rate decreases down to *10 % of its initial value with a decay time of *15 s, and this decrease in the replenishment rate significantly contributes to synaptic depression. In conclusion, the fractional release is [Ca ?? ] odependent and stimulation-independent, whereas the replenishment rate is [Ca ?? ] o -independent and stimulation-dependent.

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“…In particular this issue has received recent and strong support from two papers looking at CNS and NMJ synapses [26,27].…”

Section: Table (1) Rrp and Docked Vesicle Analysismentioning

confidence: 99%

Presynaptic Depression in Phasic Motor Nerve Terminals and Influence of 5-HT on Vesicle Dynamics

Johnstone¹,

Kellie²,

Cooper³

2008

TONEURJ

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Synaptic depression that is induced by electrical stimulation of the glutamatergic neuromuscular junction (NMJ) of the crayfish can be offset by recruitment of vesicles from a presynaptic reserve pool. This recruitment occurs following treatment of the NMJ with serotonin (5-HT), which results in a delay in the onset of synaptic depression induced by high frequency stimulation. The results of this study demonstrate that the releasable vesicles are insufficiently replenished during high frequency stimulation and that the readily releasable pool of vesicles (RRP) can be enhanced by the reserve pool (RP) in the presence of 5-HT. Anatomical visualization of vesicular pools by transmission electron microscopy after depression or during 5-HT treatment showed no differences in the number of docked and RRP vesicles. We propose that the RRP vesicles can recycle empty and that a role for 5-HT might be to induce a rapid enhancement of synaptic transmission during synaptic fatigue.

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Synaptic Vesicle Mobility in Mouse Motor Nerve Terminals with and without Synapsin

Cited by 82 publications

References 57 publications

A New Kinetic Framework for Synaptic Vesicle Trafficking Tested in Synapsin Knock-Outs

A New Kinetic Framework for Synaptic Vesicle Trafficking Tested in Synapsin Knock-Outs

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Presynaptic Depression in Phasic Motor Nerve Terminals and Influence of 5-HT on Vesicle Dynamics

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