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L L Voronin

Publications and source records attributed to L L Voronin.

At least 19 recordsLinked to original sources
PubMed2005

Ephaptic feedback in identified synapses in mollusk neurons.

The possible existence of intrasynaptic ephaptic feedback in the invertebrate CNS was studied. Intracellular recordings were made of excitatory postsynaptic potentials and currents arising on activation of the recently described monosynaptic connection between identified neurons in the snail CNS. In the presence of ephaptic feedback, tetanization of the postsynaptic neuron with hyperpolarizing impulses should activate presynaptic calcium channels, thus increasing the amplitude of excitatory postsynaptic potential, while sufficiently strong postsynaptic hyperpolarization applied during generation of the excitatory postsynaptic current should induce "supralinear" increases in its amplitude, as has been observed previously in rat hippocampal neurons. The first series of experiments involved delivery of 10 trains of hyperpolarizing postsynaptic impulses (40-50 mV, duration 0.5 sec, frequency 1 Hz, train duration 45 sec); significant changes in the amplitude of excitatory postsynaptic were not seen. In the second series of experiments, changes in the amplitude of the excitatory postsynaptic current were studied during hyperpolarization of the postsynaptic neuron. At a potential of -100 mV, the amplitude of the excitatory postsynaptic current increased significantly more than predicted by its "classical" linear relationship with membrane potential. This "supralinear" increase in the amplitude of the excitatory postsynaptic potential can be explained by the operation of ephaptic feedback and is the first evidence for this phenomenon in CNS synapses of invertebrates.

Animals↗
PubMed2004

Postsynaptic depolarisation enhances transmitter release and causes the appearance of responses at "silent" synapses in rat hippocampus.

Recent data indicate that most "silent" synapses in the hippocampus are "presynaptically silent" due to low transmitter release rather than "postsynaptically silent" due to "latent" receptors of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type (AMPARs). That synapses bearing only N-methyl-d-aspartate (NMDAR) receptors do exist is suggested by the decreased number of transmission failures during postsynaptic depolarisation and by the presence of NMDA-mediated excitatory postsynaptic currents (EPSCs) in synapses silent at rest. We tested whether these effects could be due to potentiated transmitter release at depolarised postsynaptic potentials rather than removal of Mg(2+) block from NMDARs. Using whole-cell recordings of minimal EPSCs from CA1 and CA3 neurones of hippocampal slices we confirmed decreased incidence of failures at +40 mV as compared with -60 mV. This effect was associated with a gradual increase of EPSC amplitude after switching to +40 mV and with a decrease of paired-pulse facilitation. In initially silent synapses, potentiation of pharmacologically isolated AMPAR-mediated EPSCs was still observed at +40 mV and this persisted after stepping back to -60 mV. All above effects were blocked when the cell was dialysed with the Ca(2+) chelator BAPTA (20 mM). These observations are difficult to reconcile with the "latent AMPAR" hypothesis and suggest an alternative explanation, namely that the reduction in failure rates at positive potentials is due to potentiation of transmitter release following Ca(2+) influx through NMDARs. Our results suggest that silent synapses can be mainly "presynaptically" rather than "postsynaptically silent" and thus increased transmitter release rather than insertion of AMPARs is a major mechanism of early long-term potentiation maintenance.

Animals↗
PubMed2004

Stimulation of the lateral hypothalamus provokes the initiation of robust long-term potentiation of the thalamo-cortical input to the barrel field of the adult, freely moving rat.

Long-term potentiation in the thalamo-cortical input to the somatosensory cortex barrel field has been reported to be inducible in vitro only during a narrow critical period of the first postnatal week. Here we explored whether this is due to inability of adult synapses to express LTP or lack of appropriate conditions for LTP induction in slice preparations. We recorded thalamo-cortical field potentials (FPs) from the barrel field of chronically prepared adult rats. In the first series, several parameters of conditioning tetanization of thalamus (T) have been tried. Statistically significant LTP of 135-150% relative to the baseline was observed only in rare cases (3/18) so that the mean changes were not statistically significant. In the second series, five trains of 100 Hz stimulation of T were paired with a "reinforcing" stimulation of the lateral hypothalamus (LH). In most cases (9/13), thalamo-cortical FPs were potentiated. The mean post-tetanic amplitude was 238 +/- 42% (+/- SEM) relative to the baseline (n = 13). The potentiation persisted for >1 h and typically even further increased when tested 24-48 h later. LTP magnitude strongly correlated with the initial paired-pulse ratio (PPR, coefficient of correlation r = 0.98) so that the LTP magnitude was larger (333 +/- 107, n = 6) in cases with PPR > 1.3. The mean PPR tended to decrease after LTP (from 2.05 to 1.65). Altogether the results suggest that LTP is inducible in the thalamo-cortical input to the barrel field of normal adult rats. The dependence of the LTP magnitude upon the initial PPR suggests that inputs with low initial release probability undergo larger LTP. Together with the tendency to a decrease in the PPR this suggests an involvement of presynaptic mechanisms in the maintenance of neocortical LTP.

Animals↗
PubMed2003

Low-frequency depression of synaptic responses recorded from rat visual cortex.

To characterize the low-frequency depression (LFD) of synaptic transmission in the visual cortex, we recorded field potentials and minimal excitatory postsynaptic potentials (EPSPs) from layer II/III following intracortical stimulation at various frequencies in cortical slices of rats. Field potentials were stable at 0.017 Hz, but showed an amplitude depression at 0.033-0.1 Hz at stimulus intensity of 1.5 times the threshold for induction of the postsynaptic component and at 0.1-0.2 Hz at intensity of 1.2 times the threshold. The LFD was input-specific and its magnitude correlated with the stimulus frequency. An interruption of stimulation for 15 min yielded a nearly complete recovery from LFD. Minimal EPSPs tested at 0.1-1.7 Hz often showed LFD with similar features. However, some inputs were stable or even facilitated during repeated stimulation. At 0.1 and 0.2 Hz, >50% of inputs were stable, whereas 10% and 25% were depressed, respectively. At 0.5 and 1.7 Hz, LFD was observed in >60% and 80% of inputs, respectively. The magnitude of LFD strongly varied across inputs. In 3 of the 41 inputs analyzed, LFD was so strong that these inputs became virtually silent. Occurrence of responses to the second pulse in the paired-pulse paradigm when the first response was absent and recovery of depressed EPSPs following stimulus interruption or shift to a lower frequency suggest that these synapses were presynaptically silent due to a lowered probability of transmitter release. Altogether, the results indicate that testing intervals of <10 or even < or =30 s cannot be regarded as completely neutral. At the single-cell level, frequency-dependent changes were strongly heterogeneous across different inputs. LFD and its spontaneous recovery may underlie the previously described "post-rest" potentiation, and should be taken into account when considering information processing in cortical networks.

Animals↗
PubMed2002

Quantal analysis suggests strong involvement of presynaptic mechanisms during the initial 3 h maintenance of long-term potentiation in rat hippocampal CA1 area in vitro.

Long-term potentiation (LTP) is the most prominent model to study neuronal plasticity. Previous studies using quantal analysis of an early stage of LTP in the CA1 hippocampal region (<1 h after induction) suggested increases in both the mean number of transmitter quanta released by each presynaptic pulse (m, quantal content) and postsynaptic effect of a single quantum (v, quantal size). When LTP was large, it was m that increased predominantly suggesting prevailing presynaptic contribution. However, LTP consists of several temporary phases with presumably different mechanisms. Here we recorded excitatory postsynaptic potentials from CA1 hippocampal slices before and up to 3.5 h after LTP induction. A new version of the noise deconvolution revealed significant increases in m with smaller and often not statistically significant changes in v. The changes in m were similar for both early (<1 h) and later (1-3 h) post-tetanic periods and correlated with LTP magnitude. The coefficient of variation of the response amplitude and the number of failures decreased during both early and late post-tetanic periods. The results suggest that both early (<0.5 h) and later LTP components (0.5-3 h) are maintained by presynaptic changes, which include increases in release probabilities and the number of effective release sites. In addition initially silent synapses can be converted into effective ones due to either pre- or postsynaptic rearrangements. If this occurs, our data indicate that the number and the efficacy of the receptors in the new transmission sites are approximately similar to those in the previously effective sites.

Animals↗
PubMed2001

Presynaptic R-type calcium channels contribute to fast excitatory synaptic transmission in the rat hippocampus.

The possibility that R-type calcium channels contribute to fast glutamatergic transmission in the hippocampus has been assessed using low concentrations of NiCl(2) and the peptide toxin SNX 482, a selective antagonist of the pore-forming alpha(1E) subunit of R-type calcium channel. EPSPs or EPSCs were recorded in the whole-cell configuration of the patch-clamp technique mainly from CA3 hippocampal neurons. Effects of both NiCl(2) and SNX 482 were tested on large (composite) EPSCs evoked by mossy and associative-commissural fiber stimulation. NiCl(2) effects were also tested on minimal EPSPs-EPSCs. Both substances reduced the amplitude of EPSPs-EPSCs. This effect was associated with an increase in the number of response failures of minimal EPSPs-EPSCs, an enhancement of the paired-pulse facilitation ratios of both minimal and composite EPSCs, and a reduction of the inverse squared coefficient of variation (CV(-2)). The reduction of CV(-2) was positively correlated with the decrease in EPSC amplitude. The inhibitory effect of NiCl(2) was occluded by SNX 482 but not by omega-conotoxin-MVIIC, a broad-spectrum antagonist thought to interact with N- and P/Q-type calcium channels, supporting a specific action of low concentrations of NiCl(2) on R-type calcium channels. Together, these observations indicate that both NiCl(2) and SNX 482 act at presynaptic sites and block R-type calcium channels with pharmacological properties similar to those encoded by the alpha(1E) gene. These channels are involved in fast glutamatergic transmission at hippocampal synapses.

Animals↗
PubMed2001

[Long-term potentiation of AMPA- and NMDA-components of minimal postsynaptic currents in CA1 area of the rat hippocampus].

Excitatory postsynaptic currents (EPSC) were recorded from pyramidal neurons of the rat hippocampal slices as well as the AMPA and NMDA components. A strong enough correlation between the amplitudes of the components provided a reliable evidence of their generation by the same synapse. Both components revealed similar LTP following afferent tetanisation. The data obtained do not support postsynaptic mechanisms of the LTP maintenance but suggest that increased presynaptic release represents a basic mechanism of the early LTP maintenance.

Animals↗
PubMed2000

Silent synapses in the developing hippocampus: lack of functional AMPA receptors or low probability of glutamate release?

At early developmental stages, silent synapses have been commonly found in different brain areas. These synapses are called silent because they do not respond at rest but are functional at positive membrane potentials. A widely accepted interpretation is that N-methyl-d-aspartate (NMDA) but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are functionally expressed on the subsynaptic membrane. Here we show that, in both CA3 and CA1 hippocampal regions, AMPA-mediated synaptic responses can be detected already at early stages of postnatal development. However, some synapses appear silent because of a very low probability of glutamate release. They can be converted into functional ones by factors that enhance release probability such as paired-pulse stimulation, increasing the temperature or cyclothiazide (CTZ), a drug that blocks AMPA receptor desensitization and increases transmitter release. Conversely, conducting synapses can be switched off by increasing the frequency of stimulation. Although we cannot exclude that "latent AMPA receptors" can become functional after activity-dependent processes, our results clearly indicate that, in the neonatal hippocampus, a proportion of glutamatergic synaptic connections are presynaptically rather than postsynaptically silent.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Postsynaptic hyperpolarization increases the strength of AMPA-mediated synaptic transmission at large synapses between mossy fibers and CA3 pyramidal cells.

In chemical synapses information flow is polarized. However, the postsynaptic cells can affect transmitter release via retrograde chemical signaling. Here we explored the hypothesis that, in large synapses, having large synaptic cleft resistance, transmitter release can be enhanced by electrical (ephaptic) signaling due to depolarization of the presynaptic release site induced by the excitatory postsynaptic current itself. The hypothesis predicts that, in such synapses, postsynaptic hyperpolarization would increase response amplitudes "supralinearly", i.e. stronger than predicted from the driving force shift. We found supralinear increases in the amplitude of minimal excitatory postsynaptic potential (EPSP) during hyperpolarization of CA3 pyramidal neurons. Failure rate, paired-pulse facilitation, coefficient of variation of the EPSP amplitude and EPSP quantal content were also modified. The effects were especially strong on mossy fiber EPSPs (MF-EPSPs) mediated by the activation of large synapses and identified pharmacologically or by their kinetics. The effects were weaker on commissural fiber EPSPs mediated by smaller and more remote synapses. Even spontaneous membrane potential fluctuations were associated with supralinear MF-EPSP increases and failure rate reduction. The results suggest the existence of a novel mechanism for retrograde control of synaptic efficacy from postsynaptic membrane potential and are consistent with the ephaptic feedback hypothesis.

Animals↗
PubMed2000

Differences in amplitude-voltage relations between minimal and composite mossy fibre responses of rat CA3 hippocampal neurons support the existence of intrasynaptic ephaptic feedback in large synapses.

Computer simulations and electrophysiological experiments have been performed to test the hypothesis on the existence of an ephaptic interaction in purely chemical synapses. According to this hypothesis, the excitatory postsynaptic current would depolarize the presynaptic release site and further increase transmitter release, thus creating an intrasynaptic positive feedback. For synapses with the ephaptic feedback, computer simulations predicted non-linear amplitude-voltage relations and voltage dependence of paired-pulse facilitation. The deviation from linearity depended on the strength of the feedback determined by the value of the synaptic cleft resistance. The simulations showed that, in the presence of the intrasynaptic feedback, recruitment of imperfectly clamped synapses and synapses with linear amplitude-voltage relations tended to reduce the non-linearity and voltage dependence of paired-pulse facilitation. Therefore, the simulations predicted that the intrasynaptic feedback would particularly affect small excitatory postsynaptic currents induced by activation of electrotonically close synapses with long synaptic clefts. In electrophysiological experiments performed on hippocampal slices, the whole-cell configuration of the patch-clamp technique was used to record excitatory postsynaptic currents evoked in CA3 pyramidal cells by activation of large mossy fibre synapses. In accordance with the simulation results, minimal excitatory postsynaptic currents exhibited "supralinear" amplitude-voltage relations at hyperpolarized membrane potentials, decreases in the failure rate and voltage-dependent paired-pulse facilitation. Composite excitatory postsynaptic currents evoked by activation of a large amount of presynaptic fibres typically bear linear amplitude-voltage relationships and voltage-independent paired-pulse facilitation. These data are consistent with the hypothesis on a strong ephaptic feedback in large mossy fibre synapses. The feedback would provide a mechanism whereby signals from large synapses would be amplified. The ephaptic feedback would be more effective on synapses activated in isolation or together with electrotonically remote inputs. During synchronous activation of a large number of neighbouring inputs, suppression of the positive intrasynaptic feedback would prevent abnormal boosting of potent signals.

Animals↗
PubMed1999

Triggering action potentials in an axo-dendritic inhibitory synaptic terminal.

Intracellular activity of the slow adapting neurone (SAN) was recorded together with extracellular action potentials (APs) of SAN, fast adapting neurone and inhibitory fibre in the isolated stretch receptor of the moulting crayfish. Following strychnine application, spontaneous APs and seizure-like AP trains were observed. A delay of the inhibitory fibre APs relative to SAN inhibitory postsynaptic potential, their waveforms and their initiation by intracellular SAN hyperpolarization indicate that their generation was close to the inhibitory nerve terminal. Such antidromic (ectopic) APs assert their postsynaptic action on both receptor neurones via the axon reflex. The findings provide first evidence of antidromic APs generated in the vicinity of inhibitory terminals, their direct and axon reflex-mediated action on target neurones and support a hypothesis that increased terminal excitability contributes to seizure activity.

Action Potentials↗
PubMed1999

Evidence for an ephaptic feedback in cortical synapses: postsynaptic hyperpolarization alters the number of response failures and quantal content.

The amplitude of excitatory postsynaptic potentials and currents increases with membrane potential hyperpolarization. This has been attributed to an increase in the driving force when the membrane potential deviates from the equilibrium potential of the respective ions. Here we report that in a subset of neocortical and hippocampal synapses, postsynaptic hyperpolarization affects traditional measures of transmitter release: the number of failures, coefficient of variation of response amplitudes, and quantal content, suggesting increased presynaptic release. The result is compatible with the hypothesis of Byzov on the existence of electrical (or "ephaptic") linking in purely chemical synapses. The linking, although negligible at neuromuscular junctions, could be functionally significant in influencing transmitter release at synapses with high resistance along the synaptic cleft. Our findings necessitate reconsideration of classical amplitude-voltage relations for such synapses. Thus, synaptic strength may be enhanced by hyperpolarization of the postsynaptic membrane potential. The positive ephaptic feedback could account for "all-or-none" excitatory postsynaptic potentials at some cortical synapses, large evoked and spontaneous multiquantal events and a high efficacy of large "perforated" synapses whose number increases following behavioural learning or the induction of long-term potentiation.

2-Amino-5-phosphonovalerate↗
PubMed1999

Long-term synaptic changes induced by intracellular tetanization of CA3 pyramidal neurons in hippocampal slices from juvenile rats.

Minimal excitatory postsynaptic potentials were evoked in CA3 pyramidal neurons by activation of the mossy fibres in hippocampal slices from seven- to 16-day-old rats. Conditioning intracellular depolarizing pulses were delivered as 50- or 100-Hz bursts. A statistically significant depression and potentiation was induced in four and five of 13 cases, respectively. The initial state of the synapses influenced the effect: the amplitude changes correlated with the pretetanic paired-pulse facilitation ratio. Afferent (mossy fibre) tetanization produced a significant depression in four of six inputs, and no significant changes in two inputs. Quantal content decreased or increased following induction of the depression or potentiation, respectively, whereas no significant changes in quantal size were observed. Compatible with presynaptic maintenance mechanisms of both depression and potentiation, changes in the mean quantal content were associated with modifications in the paired-pulse facilitation ratios, coefficient of variation of response amplitudes and number of response failures. Cases were encountered when apparently "presynaptically silent" synapses were converted into functional synapses during potentiation or when effective synapses became "presynaptically silent" when depression was induced, suggesting respective changes in the probability of transmitter release. It is concluded that, in juvenile rats, it is possible to induce lasting potentiation at the mossy fibre-CA3 synapses by purely postsynaptic stimulation, while afferent tetanization is accompanied by long-lasting depression. The data support the existence not only of a presynaptically induced, but also a postsynaptically induced form of long-term potentiation in the mossy fibre-CA3 synapse. Despite a postsynaptic induction mechanism, maintenance of both potentiation and depression is likely to occur presynaptically.

Animals↗
PubMed1999

[Intrasynaptic ephaptic feedback in central synapses].

A review is given of experiments performed in the author's laboratory on slices from the rat visual cortex and hippocampus. The aim was to test the existence of the positive feedback in central synapses according to a mechanism of electrical (ephatic) linking proposed by A. L. Byzow. The hypothesis predicts that, in a subset of central synapses, artificial postsynaptic membrane potential (MP) hyperpolarization should increase the amplitude of the excitatory postsynaptic current (EPSC) and potential (EPSP) not only due to a deviation from the equilibrium potential but also due to increased presynaptic transmitter release. In a part of the experiments, we found changes in several traditional parameters of transmitter release during hyperpolarization: number of response failures, coefficient of variation of response amplitude and quantal content of minimal EPSC/EPSP. The effects were especially prominent for the giant mossy fibre-CA3 synapses. For them, "supralinear" amplitude-voltage relations at hyperpolarized membrane potentials and voltage--dependent paired--pulse facilitation ratios were found. All these "non-classical" effects disappeared when composite, rather than minimal, EPSCs were evoked. These data were consistent with simulation experiments performed on the Byzov's synaptic model with the ephaptic feedback and therefore they strengthen the hypothesis. Independent of their interpretation, the data reveal a novel feedback mechanism. The mechanism provides a possibility for the central postsynaptic neurone to control the efficacy of a subset of synapses via postsynaptic MP modifications. The mechanism can essentially increase the efficacy of large ("perforated") synapses. It explains the significance of the increased number of such synapses following experimental challenges such as leading to induction of the long-term potentiation or to behavioural conditioning.

Animals↗
PubMed1998

Principal component analysis of minimal excitatory postsynaptic potentials.

'Minimal' excitatory postsynaptic potentials (EPSPs) are often recorded from central neurones, specifically for quantal analysis. However the EPSPs may emerge from activation of several fibres or transmission sites so that formal quantal analysis may give false results. Here we extended application of the principal component analysis (PCA) to minimal EPSPs. We tested a PCA algorithm and a new graphical 'alignment' procedure against both simulated data and hippocampal EPSPs. Minimal EPSPs were recorded before and up to 3.5 h following induction of long-term potentiation (LTP) in CA1 neurones. In 29 out of 45 EPSPs, two (N=22) or three (N=7) components were detected which differed in latencies, rise time (Trise) or both. The detected differences ranged from 0.6 to 7.8 ms for the latency and from 1.6-9 ms for Trise. Different components behaved differently following LTP induction. Cases were found when one component was potentiated immediately after tetanus whereas the other with a delay of 15-60 min. The immediately potentiated component could decline in 1-2 h so that the two components contributed differently into early (< 1 h) LTP1 and later (1-4 h) LTP2 phases. The noise deconvolution techniques was applied to both conventional EPSP amplitudes and scores of separate components. Cases are illustrated when quantal size (upsilon) estimated from the EPSP amplitudes increased whereas upsilon estimated from the component scores was stable during LTP1. Analysis of component scores could show apparent double-fold increases in upsilon which are interpreted as reflections of synchronized quantal releases. In general, the results demonstrate PCA applicability to separate EPSPs into different components and its usefulness for precise analysis of synaptic transmission.

Algorithms↗
PubMed1998

Interaction between paired-pulse facilitation and long-term potentiation of minimal excitatory postsynaptic potentials in rat hippocampal slices: a patch-clamp study.

Long-term potentiation is an experimental paradigm used to study synaptic plasticity and memory mechanisms. One similarity between long-term potentiation and memory is the existence of several distinct phases. However, our preliminary quantal analysis did not reveal essential differences in expression mechanisms of the early (< 1 h) and later (up to 3 h) phases of long-term potentiation. The data were compatible with presynaptic mechanisms of both phases. Another approach to distinguish between presynaptic and postsynaptic mechanisms is analysis of interaction between long-term potentiation and presynaptic paired-pulse facilitation. Such analysis had been previously done mainly with recordings of field potentials reflecting the activity of large neuronal populations. Only the early potentiation phase had been previously analysed with recordings from single neurons. The results from different groups were contradictory. In the present study, minimal excitatory postsynaptic potentials were recorded from CA1 pyramidal neurons of rat hippocampal slices. Paired-pulse facilitation ratios were calculated for various periods (up to 2-3 h) following induction of long-term potentiation. The ratio persistently decreased in the majority of neurons following long-term potentiation induction. The decrease in the paired-pulse facilitation ratio correlated with the magnitude of long-term potentiation and with the initial (pretetanic) facilitation ratio. Therefore, the general results of the present analysis was similar with the results of the quantal analysis: it is consistent with a strong involvement of presynaptic mechanisms in maintenance of both early and late phases of long-term potentiation. However, individual neurons could show variable changes in the paired-pulse facilitation, e.g., increases at late (> 0.5-1 h) periods after tetanus. Calculations of partial correlations and regression analysis indicated that positive correlation between potentiation magnitude and initial (pretetanic) paired-pulse facilitation tended to increase in the late potentiation phase (1.5-2.5 h post-tetanus) indicating that different mechanisms are involved in the early (0.5 h post-tetanus) and the late phase of long-term potentiation. The findings are compatible with involvement of presynaptic mechanisms in both the early and late phases of long-term potentiation. However, the results suggest that contribution of changes in release probability and in effective number of transmitter release sites may differ during the two phases. It is suggested that activation of silent synapses and increases in the number of transmission zones due to pre- and postsynaptic structural rearrangements represent important mechanisms of the late phase of long-term potentiation.

Animals↗