Effects of variance in mini amplitude on stimulus-evoked release: a comparison of two models

Frerking, Matthew; Wilson, Martin

doi:10.1016/s0006-3495(96)79774-6

Cited by 40 publications

(55 citation statements)

References 52 publications

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“…The distribution of miniature amplitudes was skewed to the right, as has been reported for other synapses (Bekkers et al, 1990;Frerking and Wilson, 1996) and could be well fit by an equation based on a Gaussian distribution of synaptic vesicle diameters (Bekkers et al, 1990). The mean mini amplitude in 20 cultures ranged from 0.35 to 1.42 mV (mean 0.717 Ϯ 0.272 SD), with a coefficient of variation (cv) that ranged from 0.52 to 0.99 (mean 0.699 Ϯ 0.125 SD).…”

Section: Methodssupporting

confidence: 67%

“…18 of Frerking and Wilson (1996), modified by dividing the numerator and denominator of their left-hand term by m 2 , the square of the quantal amplitude in their notation] where V and M are the variance and the mean of the PSP, q is the quantal amplitude, cv is the coefficient of variation of the quantal amplitude, and W is the fraction (which can range from 0 to 1) of the quantal variance that originates from intrasite variability. The two extreme cases occur when all of the variability is either intrasite or intersite.…”

Section: Methodsmentioning

confidence: 99%

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Switching Off and On of Synaptic Sites atAplysiaSensorimotor Synapses

2000

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Using the highly plastic synapses between mechanoreceptor sensory neurons and siphon motor neurons of Aplysia as a model, we have investigated whether switching off and on of individual synaptic release sites is a strategy that is used by neurons in forms of short-term synaptic modulation with a time course of minutes to hours. We have modified some of the techniques of classical quantal analysis and examined the kinetics of synaptic depression under different stimulation protocols to answer this question. Our analysis shows that both synaptic depression caused by homosynaptic activity and synaptic facilitation induced by an endogenous facilitatory transmitter occur by means of the shutting off and turning on, respectively, of synaptic sites, without intermediate changes in the probability of release. Our findings imply that other forms of plasticity at these synapses, such as post-tetanic potentiation, long-term facilitation, and long-term potentiation, are also expressed by all-or-none changes in activity at individual sites. We thus show that in addition to the mechanisms of synaptic integration that are known to operate in single cells and networks, neurons can exercise a further layer of fine control, at the level of individual release sites.Key words: synaptic transmission; synaptic plasticity; synaptic depression; synaptic facilitation; transmitter release; quantal analysis; miniature synaptic potentials Synaptic phenomena such as long-term potentiation and depression represent cellular mechanisms that may contribute to learning (McKernan and Shinnick-Gallagher, 1997;Murphy and Glanzman, 1997;Rogan et al., 1997), as do short-term processes such as homosynaptic depression and heterosynaptic facilitation (Zucker, 1972;Byrne et al., 1993;Cohen et al., 1997). Although detailed mechanistic explanations for these phenomena are lacking, evidence has been marshalled for such general possibilities as changes in the probability of neurotransmitter release (Bolshakov and Siegelbaum, 1994;Stevens and Wang, 1994) or the insertion or activation of postsynaptic receptors (Isaac et al., 1995;Liao et al., 1995). Other studies have reported that some synapses release no neurotransmitter initially but can be recruited by various treatments (Wojtowicz et al., 1991;Charpier et al., 1995;Wang et al., 1996). We have taken advantage of the favorable properties of sensorimotor synapses of Apl ysia to examine whether shifting of synapses into and out of the active pool occurs in short-term synaptic plasticity.Modulation of sensorimotor transmission in Apl ysia contributes to changes in its responsiveness to tactile stimulation (Carew et al., 1983;Byrne et al., 1993;Stopfer and C arew, 1996;Cohen et al., 1997). Homosynaptic depression is a progressive decline in transmitter release that occurs even at low stimulation frequency (C astellucci and Kandel, 1974). Heterosynaptic facilitation is the increase in transmitter release, mediated by facilitatory transmitters such as serotonin (5HT), that follows a noxious stimulus (Brunelli e...

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Section: Methodssupporting

confidence: 67%

Section: Methodsmentioning

confidence: 99%

Switching Off and On of Synaptic Sites atAplysiaSensorimotor Synapses

2000

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“…The theoretical relationship for a synaptic connection with non-uniform Pr and non-uniform q but with no correlation between these two parameters is shown in eqn (8) (see Frerking &Wilson 1996):…”

Section: Nmmentioning

confidence: 99%

“…These two types of quantal variance affect the relationship between variance (or CV) and synaptic conductance in different ways (Wahl, Stratford, Larkman & Jack, 1995;Frerking & Wilson 1996; see also Sigworth, 1980, for equivalent situation with ion channel subconductance levels), and can complicate the interpretation of quantal parameters estimated with the binomial model. At high release probabilities (Pr 1), only variance arising from intrasite quantal variation remains.…”

Section: Extension Of the Simple Binomial Model To Include Variabilitmentioning

confidence: 99%

“…With this approach, which we term 'multiple-probability fluctuation analysis' (MPF analysis), quantal parameters are estimated from synaptic current fluctuations measured over a wide range of experimentally imposed release probabilities at the same input. This method, which is also related to non-stationary fluctuation analysis of ion channels (Sigworth, 1980;Traynelis, Silver & Cull-Candy, 1993;Silver, Cull-Candy & Takahashi, 1996) and to a method recently suggested by Frerking & Wilson (1996), provides estimates for the underlying quantal parameters with minimal assumptions. Furthermore, it can provide estimates of N, q and the mean release probability when both the quantal size and release probability are non-uniform.…”

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confidence: 99%

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Locus of frequency‐dependent depression identified with multiple‐probability fluctuation analysis at rat climbing fibre‐Purkinje cell synapses

Silver

Momiyama

Cull-Candy

1998

The Journal of Physiology

269

306

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1. EPSCs were recorded under whole-cell voltage clamp at room temperature from Purkinje cells in slices of cerebellum from 12-to 14-day-old rats. EPSCs from individual climbing fibre (CF) inputs were identified on the basis of their large size, paired-pulse depression and all-ornone appearance in response to a graded stimulus. 2. Synaptic transmission was investigated over a wide range of experimentally imposed release probabilities by analysing fluctuations in the peak of the EPSC. Release probability was manipulated by altering the extracellular [Ca¥] and [Mg¥]. Quantal parameters were estimated from plots of coefficient of variation (CV) or variance against mean conductance by fitting a multinomial model that incorporated both spatial variation in quantal size and non-uniform release probability. This 'multiple-probability fluctuation' (MPF) analysis gave an estimate of 510 ± 50 for the number of functional release sites (N) and a quantal size (q) of 0·5 ± 0·03 nS (n = 6). 3. Control experiments, and simulations examining the effects of non-uniform release probability, indicate that MPF analysis provides a reliable estimate of quantal parameters. Direct measurement of quantal amplitudes in the presence of 5 mÒ Sr¥, which gave asynchronous release, yielded distributions with a mean quantal size of 0·55 ± 0·01 nS and a CV of 0·37 ± 0·01 (n = 4). Similar estimates of q were obtained in 2 mÒ Ca¥ when release probability was lowered with the calcium channel blocker Cd¥. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1 ìÒ) reduced both the evoked current and the quantal size (estimated with MPF analysis) to a similar degree, but did not affect the estimate of N. 4. We used MPF analysis to identify those quantal parameters that change during frequencydependent depression at climbing fibre-Purkinje cell synaptic connections. At low stimulation frequencies, the mean release probability ( − Pr) was unusually high (0·90 ± 0·03 at 0·033 Hz, n = 5), but as the frequency of stimulation was increased, − Pr fell dramatically (0·02 ± 0·01 at 10 Hz, n = 4) with no apparent change in either q or N. This indicates that the observed 50-fold depression in EPSC amplitude is presynaptic in origin. 5. Presynaptic frequency-dependent depression was investigated with double-pulse and multiple-pulse protocols. EPSC recovery, following simultaneous release at practically all sites, was slow, being well fitted by the sum of two exponential functions (time constants of 0·35 ± 0·09 and 3·2 ± 0·4 s, n = 5). EPSC recovery following sustained stimulation was even slower. We propose that presynaptic depression at CF synapses reflects a slow recovery of release probability following release of each quantum of transmitter. 6. The large number of functional release sites, relatively large quantal size, and unusual dynamics of transmitter release at the CF synapse appear specialized to ensure highly reliable olivocerebellar transmission at low frequencies but to limit transmission at higher frequencies.7697

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Differences in uniquantal amplitude between sites reduce uniquantal variance when few release sites are active

Frerking

Wilson

1999

Synapse

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In many types of central neurons, the coefficient of variation (CV) of stimulus-evoked uniquantal events inferred from quantal analysis is small, frequently less than 20%. In contrast, spontaneous putative uniquantal events (minis) from the same neurons are much more variable in amplitude, having a CV of roughly 50% or more. One explanation for this discrepancy is that, if the variance in mini amplitude were generated by differences between release sites, the small number of sites activated during stimulation would sometimes fortuitously have similar quantal amplitudes. Only in these fortuitous cases where uniquantal variance is small could quantal peaks be resolved, and therefore the uniquantal CV seen in the subset of cells where quantal analysis can be performed would systematically be much smaller than predicted by the mini distribution. We have explored this possibility by Monte Carlo simulation assuming all variance in mini amplitude to be due to intersite differences in uniquantal amplitude. We find that when a small number of release sites are activated under these conditions, there is a reduction in the expected uniquantal variance. However, the expected uniquantal CV is highly variable from one experiment to the next, and low uniquantal CVs are not expected to be seen often enough to account for the high frequency with which quantal peaks with a uniquantal CV < 20% are observed experimentally. We conclude that variance in mini amplitude between release sites cannot account for the small uniquantal CV seen in quantal analysis of many central synapses.

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Effects of variance in mini amplitude on stimulus-evoked release: a comparison of two models

Cited by 40 publications

References 52 publications

Switching Off and On of Synaptic Sites atAplysiaSensorimotor Synapses

Switching Off and On of Synaptic Sites atAplysiaSensorimotor Synapses

Locus of frequency‐dependent depression identified with multiple‐probability fluctuation analysis at rat climbing fibre‐Purkinje cell synapses

Differences in uniquantal amplitude between sites reduce uniquantal variance when few release sites are active

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