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L L Voronin

Publications and source records attributed to L L Voronin.

At least 19 recordsLinked to original sources

Noise deconvolution based on the L1-metric and decomposition of discrete distributions of postsynaptic responses.

A statistical approach to analysis of amplitude fluctuations of postsynaptic responses is described. This includes (1) using a L1-metric in the space of distribution functions for minimisation with application of linear programming methods to decompose amplitude distributions into a convolution of Gaussian and discrete distributions; (2) deconvolution of the resulting discrete distribution with determination of the release probabilities and the quantal amplitude for cases with a small number (< 5) of discrete components. The methods were tested against simulated data over a range of sample sizes and signal-to-noise ratios which mimicked those observed in physiological experiments. In computer simulation experiments, comparisons were made with other methods of 'unconstrained' (generalized) and constrained reconstruction of discrete components from convolutions. The simulation results provided additional criteria for improving the solutions to overcome 'over-fitting phenomena' and to constrain the number of components with small probabilities. Application of the programme to recordings from hippocampal neurones demonstrated its usefulness for the analysis of amplitude distributions of postsynaptic responses.

Animals

Changes in paired-pulse facilitation correlate with induction of long-term potentiation in area CA1 of rat hippocampal slices.

The phenomenon of long-term potentiation is widely used as an experimental model of memory. An approach that has been used to study its underlying mechanisms is to analyse its interaction with presynaptic paired-pulse facilitation. Several studies found no evidence for an interaction in the CA1 hippocampal area, whereas other data, for example from quantal analysis, suggested that presynaptic mechanisms contribute to the maintenance of long-term potentiation. In the present study, initial slopes of field potentials in area CA1 were measured in rat hippocampal slices. "Conventional" long-term potentiation was induced by high-frequency (100 Hz) afferent tetanization of the testing input. "Associative" long-term potentiation was induced by combining lower frequency (40 Hz) tetanization of a testing input with high-frequency tetanization of a second input. The paired-pulse facilitation ratio decreased in the majority of experiments in which long-term potentiation was induced conventionally, but it decreased, increased or did not change after inducing associative potentiation. Decreases in the paired-pulse facilitation correlated inversely with the initial (pre-tetanic) facilitation ratio. A more detailed regression analysis suggests that this correlation results from two other correlations: (i) that between changes in paired-pulse facilitation and the magnitude of long-term potentiation, and (ii) that between initial paired-pulse facilitation and the magnitude of long-term potentiation. The first correlation prevailed during the initial 10 min following tetanization, while the second prevailed 40-60 min later. A post-tetanic decrease in paired-pulse facilitation is evidence for an involvement of presynaptic mechanisms in the maintenance of long-term potentiation. The lack of significant changes in some studies could be due to the inclusion in the analyses of experiments with long-term potentiation of small magnitude, in which changes in paired-pulse facilitation ratios would have been inconsistent. The present study suggests that the early (10-20 min) and late (40-50 min) phases of long-term potentiation were mediated by different mechanisms, with a mixture of these mechanisms during the intermediate period. On the basis of the present and previous studies, the following scheme of involvement of several mechanisms in long-term potentiation maintenance is proposed. The early phase includes two major mechanisms: an increase in the probability of transmitter release, leading to an apparent increase in the number of effective release sites, and an increase in efficacy of one transmitter quantum, probably due to an increased number of postsynaptic receptors. The later phase of long-term potentiation is attributed to an increase in the number of transmitter zones, presumably due to structural modifications.

Animals

Involvement of silent synapses in the induction of long-term potentiation and long-term depression in neocortical and hippocampal neurons.

Changes in the latency of small excitatory postsynaptic potentials were observed in association with induction of long-term modifications of synaptic transmission in slices of rat neocortex and guinea-pig hippocampus. After potentiation response latency decreased in 3/10 cases in the neocortex and in 6/24 cases in the hippocampus, and increased after depression in 4/8 cases in the neocortex. These latency changes could not be attributed to changes in presynaptic fibre excitability, monosynaptic inhibition, release kinetics or activation kinetics of postsynaptic ion channels. We conclude therefore that potentiation led to the activation of previously silent synapses of fast-conducting afferents and depression to the inactivation of previously functional synapses. Thus, neocortical and hippocampal synapses can be in a non-functional state, and regimes that induce long-term potentiation and depression not only change the efficacy of synapses but also alter their functional state.

Animals

All-or-none excitatory postsynaptic potentials in the rat visual cortex.

Intracellular recordings were obtained from supragranular neurons in slices of the rat visual cortex. In approximately 25% of the cells large (0.5-1.6 mV) excitatory postsynaptic potentials (EPSPs) of constant amplitude were observed after minimal, presumably single-fibre stimulation. The amplitude variance of these large EPSPs was surprisingly small and within the range of the variance of the noise. These EPSPs could be reduced in amplitude by paired-pulse and low-frequency stimulation or by raising extracellular Mg2+ concentration. Reduced EPSPs could either continue to behave as all-or-none responses, or they could fluctuate between several amplitude levels. Conversely, responses where the amplitude fluctuated from trial to trial under control conditions could be converted into large all-or-none responses by paired-pulse facilitation. This indicates that the large all-or-none EPSPs were composed of several subunits, probably reflecting the action of several different release sites. It is concluded that these release sites are either independent and operate with a probability close to 1 or, if operating with a lower probability, are coordinated by a mechanism which synchronizes release. Several observations suggest that release probabilities can switch from values close to 1 to 0 with repetitive stimulation or high Mg2+ concentration. Thus, a substantial fraction of single-fibre inputs to supragranular cells possess synapses which operate with high synaptic efficiency and extremely low variance under control conditions but can undergo drastic changes in efficacy when release probabilities are interfered with. Such modifications of release probability could serve as an effective mechanism to regulate the gain of synaptic transmission.

Animals

Postsynaptic induction of long-term synaptic facilitation in snail central neurones.

Long-term facilitation in molluscs is believed to be induced due to purely presynaptic activations. We recorded excitatory postsynaptic potentials (EPSPs) simultaneously from two identified neurones of snail parietal ganglia. We report a non-decrementing facilitation induced by intracellular tetanization with concomitant presynaptic activation. The mean EPSP amplitude measured in 10 neurones 30-50 min after tetanization was 17% greater than in the non-tetanized control neurones. Only short-lasting (5-10 min) postsynaptic changes were found (post-tetanic hyperpolarization and resistance decrease). The facilitation was especially prominent (34%, 10 min post-tetanus) but decreased within 15 min in preparations with rapid wash-out of the external media. The data suggest that induction of long-term enhancement in molluscs depends on postsynaptic events and, like in mammals, may involve increased postsynaptic Ca2+ and subsequent release of retrograde messengers.

Animals

Induction of LTP and LTD in visual cortex neurones by intracellular tetanization.

Neurones from supragranular layers of rat visual cortex slices were activated by intracellular tetanization (IT) without concomitant presynaptic stimulation. The effect of IT was examined on EPSPs evoked at low stimulation intensity from two subsets of afferents by electrodes positioned in layers II and IV, respectively. In 17 of 23 inputs to 15 cells IT led to changes in EPSP amplitudes which persisted throughout the recording period (from at least 40 min to 3 h). For 10 potentiated inputs (nine cells) and eight depressed inputs (seven cells), EPSP amplitudes measured 30 min after tetanization were 167 +/- 14% and 55 +/- 14% of the pretetanic controls, respectively. In seven cells both inputs changed, in five cases modifications were of the opposite and in two cases of the same polarity.

Animals

Interaction between paired-pulse facilitation and long-term potentiation in area CA1 of guinea-pig hippocampal slices: application of quantal analysis.

The aim of the study was to further specify mechanisms of maintenance of hippocampal long-term potentiation. Previous analysis of excitatory postsynaptic potentials showed increases in quantal content (mean number of neurotransmitter quanta released by every testing pulse) with smaller increases in quantal size (effect of one transmitter quantum) following long-term potentiation induction. Here we recorded intracellularly excitatory postsynaptic potentials from CA1 pyramidal neurons of guinea-pig hippocampal slices after minimal paired-pulse stimulation of monosynaptic inputs. Statistical parameters underlying excitatory postsynaptic potential fluctuations were estimated by a deconvolution procedure using a quantal model. The parameters of excitatory postsynaptic potentials following paired-pulse stimulation were studied before and after induction of long-term potentiation. Under both conditions, paired-pulse facilitation was found to be accompanied by increases in quantal content and quantal size. During long-term potentiation, paired-pulse facilitation of amplitude and quantal content was lower. The respective changes in the paired-pulse facilitation ratios correlated with long-term potentiation magnitude. In contrast, the paired-pulse facilitation of quantal size did not change significantly following long-term potentiation induction. The results are compatible with the existence of two separate mechanisms of long-term potentiation maintenance. They support the suggestion that changes in quantal content are mainly due to presynaptic mechanisms which are shared by long-term potentiation and paired-pulse facilitation. The mechanisms underlying changes in quantal size are of a different nature for long-term potentiation and paired-pulse facilitation. For long-term potentiation they might be located postsynaptically.

Animals

Reliability of quantal parameter estimates and their changes during long-term potentiation in guinea pig hippocampal slices.

Previously we found increases in quantal content (m) and smaller increases in quantal size (v) during long-term potentiation (LTP) in CA1 of hippocampal slices. However, the validity of the deconvolution technique was questioned recently because v estimates correlated with the noise standard deviation (Sn). In computer simulations we show a double-step dependence of v on Sn/v: correct v estimates (within +/- 20%) for Sn/v < or = 0.5 and overestimates (correlated with Sn) for Sn/v > 0.5. A novel 'noise addition' procedure is proposed for accepting reliable solutions on the basis of the double-step relationship between v and Sn. Quantal analysis of LTP for more reliable solutions confirmed previous conclusions.

Animals

Quantal parameters of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach.

Binomial distributions of amplitudes of excitatory postsynaptic potentials (EPSPs) mixed with Gaussian noise were simulated. The objective of Monte Carlo simulations was, firstly, to study influences of sampling size (N) and noise standard deviation (Sn) on estimates of mean quantal content (m), quantal size (v) and binomial parameters (n and p) by four methods of quantal analysis (histogram, variance, failures and combined method) based on the binomial model and, secondly, to modify these methods on the basis of comparison of estimated with simulated parameters. Reliable estimates (within +/- 10% of the simulated values) were obtained for large sample sizes (N = 500-1000) with Sn less than or equal to v by the histogram (deconvolution) method and with Sn less than or equal to 2v by the other three methods. Similar results were obtained by averages from about 10 simulations if smaller samples were used (N = 50-200). In electrophysiological experiments on slices, "minimal" EPSPs were recorded from CA1 pyramidal cells after low-intensity stimuli to stratum radiatum or stratum oriens. Amplitudes of minimal EPSPs fluctuated in a manner predicted by the quantum hypothesis. Amplitude distributions of EPSPs in the non-facilitated state were adequately described either by binomial statistics with an average p equal to about 0.4 (a range of 0.3-0.7) and an average n of about 3 (range 2-6) or by Poisson statistics with m of about 1. The quantal analysis suggests that typical values of m and v for a single activated fibre in stratum radiatum might be about 0.5-1 and 300-400 microV, respectively, with low p (0.1-0.3) and n (2-4). However, the estimates of binomial parameters should be considered as coarse approximations in view of the simulation results and a possible nonuniformity of parameter p. The comparison of results of various methods based on the binomial model, in both simulation and physiological experiments, indicates the reliability of estimates of basic quantal parameters (m and v) under realistic conditions of physiological experiments. The methods are considered to be sufficiently sensitive to make use of them for studies on mechanisms of long-term synaptic plasticity.

Animals

Statistical analysis of long-term potentiation of large excitatory postsynaptic potentials recorded in guinea pig hippocampal slices: binomial model.

Excitatory postsynaptic potentials (EPSPs) were recorded in guinea pig hippocampal slices (area CA1) from 15 neurons after stimulation of stratum radiatum (str. rad.) and stratum oriens. EPSP amplitudes increased in 8 neurones (10 post-tetanic regions) recorded 15 to 45 min after tetanic stimulation of str. rad. The increase was considered to represent long-term potentiation (LTP). Quantal analysis was performed by two methods assuming binomial statistics: the histogram method using deconvolution of noise and the variance method. According to both methods, LTP was associated with an increase in mean quantal content (m) which correlated with LTP magnitude. A statistically significant increase in quantal size (v) was found only by the histogram method and the increase was not correlated with LTP magnitude. A separate analysis of EPSPs with small LTP magnitude demonstrated that with the histogram method only v was increased but not m. A smaller increase in m for the pooled data of both methods did not correlate with LTP magnitude for this EPSP subset. The increase in m for the whole EPSP set corresponds to previous results on the quantal analysis of LTP in in vivo preparations and favours a presynaptic location of major mechanisms underlying LTP maintenance. The increase in v indicates the existence of another mechanism responsible for the maintenance of a small part of LTP. This mechanism might involve either pre- or postsynaptic changes or both.

Algorithms

Quantal analysis of long-term potentiation of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach.

"Minimal" excitatory postsynaptic potentials (EPSPs) were recorded from 13 neurones in area CA1 of guinea pig hippocampal slices after double-pulse stimulation of stratum radiatum (str. rad.) and stratum oriens (str. or.). Amplitudes of EPSPs significantly increased in 8 neurones 5 to 55 min after 9 tetanizations in str. rad.. The increase was considered to represent long-term potentiation (LTP). Altogether 26 EPSPs (42 post-tetanic regions) were statistically analysed by four methods of the quantum hypothesis assuming the binomial model of transmitter release: the deconvolution (histogram), the variance, the failures, and the combined (variance-failures) methods. The mean quantal content (m) significantly increased after LTP induction according to all methods used. Quantal size (v) also tended to increase but according to some methods, the increase was not statistically significant and it did not correlate with LTP magnitude. However, for an EPSP subset with a LTP magnitude of less than 1.55, the increase in v correlated with LTP magnitude, whereas the increase in m did not. The relative contribution of the increase in v to LTP magnitude was larger for cases with small LTP than for the whole EPSP set. In general, the increase in m corresponds to previous studies and favours the presynaptic location of major mechanisms of LTP maintenance, i.e. an increase in the average number of transmitter quanta released by each presynaptic volley. The post-tetanic increase in v might reflect some additional mechanisms which presumably include an increase in the amount of transmitter in one quantum.

Animals

Analysis of fluctuations of "minimal" excitatory postsynaptic potentials during long-term potentiation in guinea pig hippocampal slices.

In previous studies, quantal analysis assuming a simple binomial model has shown that long-term potentiation (LTP) is accompanied by an increase in both mean quantal content (m) and quantal size (v), whereby the increase in m predominates. In the present study, "compound" binomial distributions with variable probabilities were convolved with Gaussian distributions in computer experiments to simulate amplitude histograms of intracellular excitatory postsynaptic potentials (EPSPs). A deconvolution procedure assuming equal "quantal" separation (v) between discrete components, but without assuming binomial statistics, was applied to the simulated distributions to determine v. It was found that with a small ratio of standard deviation of noise to v (Sn/v less than 0.4), a reliable estimate of v can be obtained even for small samples (N = 100). When Sn/v was larger (0.4-0.6), approximate v estimates (within +/- 10-20% of the simulated v) could be obtained by averaging estimates from about 10 small samples (N = 100). "Minimal" EPSPs were recorded in area CA1 of guinea pig hippocampal slices. 37 EPSP amplitude samples of 9 neurones were measured before and up to 55 min after 10 tetanizations of stratum radiatum. In accordance with the previous data, the increase in v accounted for only about 10% of the average post-tetanic increase in EPSP amplitude and was not correlated with the latter. However, for an EPSP subset with small LTP magnitude, the increase in v accounted for an essential part of the LTP magnitude while the increase in m did not correlate with it. The results are in agreement with previous data obtained in the context of the simple binomial model and are interpreted as indicating primarily a presynaptic mechanism of LTP maintenance. The results suggest two types of synaptic mechanism of LTP maintenance related to the increases in m and v, respectively. The latter mechanism is saturated at about 10 to 30% increase in post-tetanic amplitude above the pre-tetanic EPSP amplitude.

Animals

[A quantum analysis of the long-term posttetanic changes in the minimal postsynaptic potentials in surviving hippocampal slices].

Excitatory postsynaptic potentials (EPSPs) were recorded in guinea pig hippocampal slices (area CA1) from 13 neurons after single or double-pulse stimulation of stratum radiatum (the Schaffer collaterals) and stratum oriens. Amplitudes of 23 EPSPs (9 neurons, 12 pathways) grew 5 to 55 min after 10 tetanic stimulations of the Schaffer collaterals. This increase has been considered as a long-term potentiation (LTP). A statistical analysis was carried out by four methods of the quantal hypothesis based on the binomial distribution. It revealed an increase in the mean quantal content (m) during LTP. An increase in the quantal size was also observed in the majority of the cases but it showed only a weak correlation with the LTP magnitude and for some methods it was statistically significant only for the periods later than 15 min after tetanic stimulation. A well expressed increase in m demonstrated by various methods corresponds to data of the previous in vivo studies and favours the presynaptic location of mechanisms of the LTP maintenance.

Animals

[Suppression of the "fast" IPSP when superimposed on the "slow" IPSP as a possible cause of priming in the mouse hippocampus].

Extra- and intracellular responses of the mouse hippocampus were recorded at CA1 region after stimulation of two independent inputs from the Schaffer collateral/commissural fibres: conditioning or priming input (C1) and testing or primed one (C2). Duration and amplitude of primed field potentials (FP) and excitatory postsynaptic potentials (EPSP) as well as amplitudes of early (IPSPa) and late (IPSPb) components of inhibitory postsynaptic potentials (IPSP) were measured with variation of C1-C2 intervals from 0 to 1 s. An increase in the FP duration as well as EPSP duration and amplitude and suppression of the IPSP amplitude occurred after conditioning with intervals of 50-500 ms, maximal effect was at 200 ms ("priming" effect). These changes correlated with the amplitude of priming IPSPb. The most prominent effect was observed in cells with hyperpolarizing IPSPa. It is assumed that primed FP and EPSP increase due to suppression of the primed IPSPa, when it is superimposed on the priming IPSPb.

Animals

[A quantal analysis of the long-term potentiation of the total postsynaptic neuronal potentials in surviving hippocampal slices].

Excitatory postsynaptic potentials (EPSPs) from 14 neurons have been recorded in hippocampal slices (area CA1) of guinea pigs after stimulation of stratum radiatum (Schaffer collaterals) and stratum oriens. An increase of EPSP amplitudes observed in 7 neurons (9 pathways) recorded 15-45 min after titanic stimulation of Schaffer collaterals is considered as a long-term potentiation (LTP). A statistical analysis in the frame of two methods of the quantal hypothesis (histogram and variance methods) has shown an increase in the mean quantal content (m) during LTP. An increase in the quantal size found only by the histogram method is considered to be less reliable because comparatively strong dependence of the histogram method on the noise level. An increase in m revealed by two methods corresponds to the previous in vivo studies and favours a presynaptic location of mechanisms responsible for the growth of the synaptic efficacy during LTP.

Animals