The kinetics of transmitter release at the frog neuromuscular junction

Barrett, Ellen F.; Stevens, Charles F.

doi:10.1113/jphysiol.1972.sp010054

Cited by 312 publications

(277 citation statements)

References 25 publications

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“…Classic experiments indicate that after trains of APs, presynaptic Ca 2ϩ accumulates, leading to a delayed or asynchronous (mini like) release of synaptic vesicles (Barrett and Stevens, 1972). Data indicate that this delayed release is proportional to the bulk (also termed residual) [Ca 2ϩ ] i (Atluri and Regehr, 1998), in contrast to the brief microdomains of [Ca 2ϩ ] i that trigger phasic release (Meinrenken et al, 2003).…”

Section: Introductionmentioning

confidence: 92%

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: Introductionmentioning

confidence: 92%

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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“…Other and more important factors may have contributed to this delay. These include the conduction time of the action potential along the axons and the dispersion in the synaptic delay time (2,3). All of these times may be prolonged over their values at 20"C as the muscle approaches the cold copper block clouded by chilled helium gas (28).…”

Section: Discussionmentioning

confidence: 99%

Temporal coincidence between synaptic vesicle fusion and quantal secretion of acetylcholine.

Torri-Tarelli¹,

Grohovaz²,

Fesce³

et al. 1985

The Journal of Cell Biology

150

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We applied the quick-freezing technique to investigate the precise temporal coincidence between the onset of quantal secretion and the appearance of fusions of synaptic vesicles with the prejunctional membrane. Frog cutaneous pectoris nerve-muscle preparations were soaked in modified Ringer's solution with 1 mM 4-aminopyridine, 10 mM Ca 2+, and 10 -4 M d-Tubocurarine and quick-frozen 1-10 ms after a single supramaximal shock. The frozen muscles were then either freeze-fractured or cryosubstituted in acetone with 13% OsO4 and processed for thin section electron microscopy. Temporal resolution of <1 ms can be achieved using a quick-freeze device that increases the rate of freezing of the muscle after it strikes the chilled copper block (15°K) and that minimizes the precooling of the muscle during its descent toward the block. We minimized variations in transmission time by examining thin sections taken only from the medial edge of the muscle, which was at a fixed distance from the point of stimulation of the nerve. The ultrastructure of the cryosubstituted preparations was well preserved to a depth of 5-10/~m, and within this narrow band vesicles were found fused with the axolemma after a minimum delay of 2.5 ms after stimulation of the nerve. Since the total transmission time to this edge of the muscle was ~3 ms, these results indicate that the vesicles fuse with the axolemma precisely at the same time the quanta are released.Freeze-fracture does not seem to be an adequate experimental technique for this work because in the well-preserved band of the muscle the fracture plane crosses, but does not cleave, the inner hydrophobic domain of the plasmalemma. Fracture faces may form in deeper regions of the muscle where tissue preservation is unsatisfactory and freezing is delayed.Neurotransmitters are released from nerve terminals in two ways: by the continuous leakage of individual molecules across the nerve terminal membrane (23,33,41,50) and by synchronous secretion of few thousands molecules in packages, or quanta (14,15,20). Quantal secretion causes the changes in membrane potential that excite the postsynaptic cell, and transmission at a synapse is critically dependent upon this mechanism of release. The vesicle hypothesis holds that each quantum is confined within one of the synaptic vesicles that populate the nerve terminal and is released by exocytosis when the membrane of that vesicle fuses with the axolemma at one of the many specialized regions called "active zones" (8,13,51).A number of workers have shown that at frog neuromuscular junctions vesicles fuse with the axolemma of stimulated 1386 terminals and some of the remaining vesicles become labeled with extracellular tracers (9)(10)(11)25). Although these observations indicate that vesicles fuse with and are recovered from the axolemma when quanta are actively secreted, the slowness of chemical fixation precludes demonstrating that vesicle fusion and transmitter release are coincident. The images of fusion seen after chemical fixation represent...

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“…The uIPSC time course is critically determined by the transmitter release time course (RTC). We therefore quantified RTC using a first-latency approach (8,26,27). The full width at half-maximum (t 50 ) of the first-latency distribution did not correlate with τ ( Fig.…”

Section: Composition Of Gaba a Receptor Subunits At Pii-gc Connectionsmentioning

confidence: 99%

Strength and duration of perisomatic GABAergic inhibition depend on distance between synaptically connected cells

Strüber

Jónás

Bartos

2015

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

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GABAergic perisoma-inhibiting fast-spiking interneurons (PIIs) effectively control the activity of large neuron populations by their wide axonal arborizations. It is generally assumed that the output of one PII to its target cells is strong and rapid. Here, we show that, unexpectedly, both strength and time course of PII-mediated perisomatic inhibition change with distance between synaptically connected partners in the rodent hippocampus. Synaptic signals become weaker due to lower contact numbers and decay more slowly with distance, very likely resulting from changes in GABA A receptor subunit composition. When distance-dependent synaptic inhibition is introduced to a rhythmically active neuronal network model, randomly driven principal cell assemblies are strongly synchronized by the PIIs, leading to higher precision in principal cell spike times than in a network with uniform synaptic inhibition.interneurons | synaptic transmission | dentate gyrus | basket cell | gamma oscillations G ABAergic parvalbumin (PV)-expressing fast-spiking perisoma-inhibiting interneurons (PIIs) provide powerful synaptic inhibition to large numbers of target cells distributed over several hundred micrometers of cortical space (1-5). Extent and density of their axonal projection together with the perisomatic location of their output synapses close to the site of postsynaptic action potential generation are thought to provide tight control over the activity of target cells. Moreover, PIIs usually interact with other PIIs by reciprocal chemical and electrical synapses, thereby forming interneuron (IN) networks (4, 6, 7), which have been proposed to orchestrate the activity of cortical circuits. PIIs have been shown to receive rapid synaptic excitation (8) and to provide fast, strong, and faithful inhibitory signals to their postsynaptic partners (3,5,6). This fast and reliable signaling phenotype has been hypothesized to support the synchronization of neuronal networks leading to rhythmic activity patterns predominantly in the gamma frequency ranges [30-50 Hz, low gamma; 50-90 Hz, midfrequency gamma; 90-150 Hz, high gamma (7, 9)]. Several lines of evidence indeed indicate that PIIs are critical for the emergence of gamma activity. PIIs discharge at high frequencies tightly phase-locked to gamma cycles in vivo (10-13), they can entrain the activity of large principal cell assemblies (2, 14, 15), and silencing them impairs cortical gamma oscillations (14, 16). Thus, fast-spiking PIIs are generally regarded as a reliably active IN type that paces activity of large principal cell populations by strong and fast uniform inhibition.However, uniformity of PII output signaling has only been assumed and never been tested experimentally. In fact, quantitative analysis of the PII axon morphology shows a gradual decline in axon collateral density with distance from the soma (17-19) frequently interpreted as a reduction in connection probability at larger distances (20, 21), comparable to observations from excitatory glutamatergic neurons in the neo...

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The kinetics of transmitter release at the frog neuromuscular junction

Cited by 312 publications

References 25 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

Temporal coincidence between synaptic vesicle fusion and quantal secretion of acetylcholine.

Strength and duration of perisomatic GABAergic inhibition depend on distance between synaptically connected cells

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