Quantal Analysis Research Articles

Inversion of He-Ne elastic-scattering data.

Quantal and semiclassical (WKB) methods of inversion have been used in an analysis of the elastic-scattering cross sections for 62.5-meV He atoms from Ne atoms by which an effective local interaction between those atoms is specified. The potentials obtained by the approximate method (WKB) differ from that found with the full quantal analysis. The quantal inversion potential is repulsive at short distances and becomes attractive at a radius of 2.695 A. It has a minimum value of [minus]1.981 meV at a radius of 2.98 A.

Quantal analysis based on spectral methods

A method for calculating quantal size based on spectral analysis of postsynaptic potential (PSP) amplitude distributions was developed and tested by Monte-Carlo techniques. It was combined with a test to reveal the bias of the estimate of quantal size and to determine whether the peaks in amplitude distributions reflect quantal release or a sampling artifact. Spectral density was computed using fast Fourier transformation after subtraction of a fitted polynomial from the probability density function. The method overestimated quantal size for values less than two standard deviations of noise, indicating that those estimates as well as estimates of quantal size computed for examples of non-quantal distributions are not reliable. This was the case for 34 of 36 sets of sensorimotor excitatory PSPs of the frog, suggesting that most values of the quanta in synapses between primary fibres and lumbar motoneurons are smaller than 70-90 microV.

Nitroprusside inhibits neurotransmitter release at the frog neuromuscular junction.

Sodium nitroprusside (SNP), when applied at concentrations ranging from 0.01 microM to 1.0 mM, reduced endplate potentials in sartorius muscle fibers of the frog (Rana pipiens) by a mean of 57% (range 37-79%). Using quantal analysis, this reduction was shown to be predominantly, if not exclusively, due to a reduction in neurotransmitter release rather than a decrease in postsynaptic sensitivity. Inhibition of neuromuscular transmission was not observed if the preparation was pretreated with bovine hemoglobin prior to the addition SNP nor if 'old' SNP solutions, in which the SNP had decomposed for at least 24 h, were applied. These results suggest that nitric oxide inhibits the evoked release of neurotransmitter at the frog neuromuscular junction.

Quantal analysis of string-inspired lineal gravity with matter fields

We show that string-inspired lineal gravity interacting with matter fields cannot be Dirac-quantized owing to the well-known anomaly in energy-momentum tensor commutators.

A theoretical framework for quantal analysis and its application to long-term potentiation.

1. We present a new mathematical description of the complete distribution of electrical responses to stochastic synaptic activity (quantal analysis) that is intended as a model of experiments on central neuronal synapses. Unlike previous treatments, this distribution is calculated for each instant after the release of transmitter into the cleft. 2. We follow the traditional description of probabilistic presynaptic vesicle release. On the postsynaptic side, however, we assume that channel fluctuations are important and we take them into account. The probability of finding a given channel open after a certain amount of transmitter is released is calculated from detailed receptor/channel and neurotransmitter clearance kinetics. This approach allows us to naturally include the nonlinear dependence of open probability on the amount of transmitter released, with saturation for large transmitter doses. The distribution of open channels is calculated from this probability. 3. We also allow the possibility that multiple synaptic inputs to a target neuron may be active in a typical experiment. We have not treated cable effects. We explore the implications of multiple synapses for the nonlinearities of the system. The most important of these is that vesicles in different synapses have independent responses, and therefore their effects add linearly. 4. The resulting distributions depend heavily on what region of the nonlinear dose-response curve the synapses are in. Far from saturation, peaks in the distribution are due to vesicles, and close to saturation they are due to active synapses. Peak widths are due to channel fluctuations and instrumental noise, which we introduce to make closer contact with experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

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-tenn 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.

Quantal analysis of synaptic transmission in the central nervous system

In the past year, important advances have been made in the understanding of quantal neurotransmission at central synapses. These include new statistical tests for the significance of quantal peaks in synaptic amplitude histograms, greater understanding of possible sources of quantal variance, and new attempts to undertake a rigorous quantal analysis of neurotransmission.

Increase in synaptic vesicle proteins accompanies long-term potentiation in the dentate gyrus

Maintenance of long-term potentiation in synapses formed by the perforant path on to granule cells of the dentate gyrus is accompanied by a sustained increase in the extracellular concentration of glutamate, 3,4 the presumed transmitter at this excitatory hippocampal pathway. Quantal analysis 2,12,13,19,27 indicates that, at least in the first hour of induction, this reflects an increase in transmitter release rather than a decrease in glutamate uptake, while biochemical studies 4,17,18 have suggested that the increase in release persists for several hours. Morphological studies have described early but persistent increases in the spine number 5,14 and area. 28 Increases in the number of segmented/perforated synapses persisting for at least 1 h after induction of long-term potentiation, have also been reported. 9,24 These morphological changes suggest both presynaptic and postsynaptic modifications. 15 Increases in synaptic vesicle number 20 and distribution 1 lasting for at least 1 h specifically indicate presynaptic changes. To explore further the role of the presynaptic terminal in long-term potentiation, we have investigated changes in three synaptic vesicle proteins, synapsin, synaptotagmin and synaptophysin, in control tissue and in tissue prepared from potentiated dentate gyrus 45 min and 3 h after induction of long-term potentiation. We found that there was an increase in the concentration of the three proteins 3 h after induction of long-term potentiation. No such increase was observed 45 min after induction or in tissue prepared from animals in which an intraventricular injection of the N-methyl- d-aspartate receptor antagonist, D(−)-2-amino-5-phosphonopentanoic acid, blocked induction of long-term potentiation. This finding demonstrates an increased expression of synaptic vesicle proteins in long-term potentiation and implies the existence of distinct temporal phases of long-term potentiation during which different synaptic mechanisms for increased transmitter release are engaged.

Amplitude fluctuations of

Quantal analysis has provided evidence for a presynaptic contribution to long-term potentiation in hippocampal CA1 cells. This however leaves unexplained the observation that long-term potentiation has little or no effect on the NMDA receptor-mediated component of the synaptic signal. Here, I report that, in baseline conditions, the coefficient of variation of the AMPA/kainate receptor-mediated signal (CV A/K) is consistently larger than that of the NMDA component (CV NMDA), a result which can be explained if AMPA/kainate receptors are absent or nonfunctional at a proportion of synapses. Long-term potentiation is associated with a reduction in CV AK, but no change in either the average amplitude of the NMDA component or CV NMDA. This is consistent with the proposal that long-term potentiation induction uncovers clusters of latent AMPA/kainate receptors, with no change in transmitter release.

Practical guidance for testing the accuracy of deconvolution results from quantal analysis.

A Monte Carlo study was carried out to test the reliability of the Maximum Likelihood Estimator (MLE) approach for quantal analysis. This widely used statistical method was applied to extract a finite mixture of Gaussian distributions from simulated data. The data were generated by convolving a distribution of discrete amplitude steps (multiples of a unitary step Q) with Gaussian noise of various standard deviations (sigma n). Our results offer practical guidance on when to use the MLE, taking into account the determining parameters: signal to noise ratio (Q/sigma n, the most important parameter), number of samples collected and the number of components (k). For a given set of parameters the algorithm always converged to the "true" values, never converged to the "true" values or converged in only a fraction of cases to the "true" values. The behavior of the fitting routine in the parameter space is displayed in contour plots. These contour plots can be used as a guide to test the accuracy of deconvolution results.

Quantal analysis of hippocampal long-term potentiation.

Long-term potentiation (LTP) is a lasting (hours, days) increase in electrical responses after brief (seconds) high-frequency activation of monosynaptic pathways. It represents a popular model to study mechanisms of learning and memory. There is a general agreement on mechanisms of LTP induction, at least for LTP in hippocampal area CA1. However, a controversy exists about mechanisms of LTP maintenance: there is evidence for both pre- and postsynaptic locations of LTP mechanisms. Publications on statistical (quantal) analysis of fluctuations of excitatory postsynaptic potentials in hippocampal and some other structures are reviewed. The analysis suggests two independent mechanisms for LTP maintenance during the first hour. They are termed LTPm and LTPv and are expressed as changes in the mean number of transmitter quanta or quantal content (m) and changes in the effect of one quantum or quantal size (v), respectively. The increased number of transmitter quanta per presynaptic impulse (LTPm) can account for the many-fold increase in synaptic efficacy during LTP, especially when initially "silent" connections increase their release probabilities (p). The increase in the number of effective release sites is considered to be secondary to the increase in p. Appearance of new subsynaptic receptors, which can produce an apparent increase in m, is not excluded. The additional mechanism (LTPv) can account for an essential part of potentiation when the LTP magnitude is relatively small (< 60% increase over pretetanic amplitude). Experiments with paired-pulse facilitation support postsynaptic mechanisms for quantization and for LTPv. Intriguing problems for future statistical analysis of quantal synaptic mechanisms for behavioral memory and conditioning are understanding the different mechanisms for induction of LTPm and LTPv, and their contribution to the maintenance of LTP during post-tetanic periods of > 1 hour.

Increased transmitter release at excitatory synapses produced by direct activation of adenylate cyclase in rat hippocampal slices

The field EPSP recorded in the CA1 region of rat hippocampal slices is potentiated by bath application of the direct adenylate cyclase activator forskolin (Chavez-Noriega and Stevens, 1992a). We have now used the whole-cell patch-clamp technique to analyze the effect of forskolin on evoked synaptic currents and on spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) recorded in rat hippocampal slices in order to determine the relative contributions of pre- and postsynaptic mechanisms to this increased synaptic strength. Application of 50 microM forskolin in the presence of 3-isobutyl-1-methylxanthine (IBMX; a phosphodiesterase inhibitor) enhanced the evoked EPSC (eEPSC) peak amplitude to 230 +/- 43% of control (n = 13). No significant change in sEPSC or in mEPSC amplitude was detected after forskolin addition (106 +/- 7%, n = 9), indicating that postsynaptic receptor sensitivity at synaptic junctions is not greatly affected. In contrast, a large increase in sEPSC and mEPSC frequency was noted in all cells (299 +/- 81%). Following forskolin application, the amplitude distribution of evoked synaptic currents shifted to larger values, but more significantly, a sharp decrease in failure rate was produced in all cells tested. Also, a significant correlation was found between the potentiation produced by forskolin in IBMX on the eEPSC and the ratio of the squared coefficient of variation (CV = SD/mean). Finally, a quantal analysis of four cells was consistent with the hypothesis that transmitter release was increased by forskolin/IBMX with, if anything, a concomitant decrease in quantal size. Together, these observations indicate that presynaptic mechanisms significantly contribute to the enhancement produced by this diterpene.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantal analysis of synaptic transmission in hippocampal and cerebellar slices

Quantal analysis of synaptic transmission in hippocampal and cerebellar slices

Block of GABA-transaminase modifies GABAergic transmission at the crayfish synapses.

1. The cytosolic concentration of a neurotransmitter is believed to be an important factor determining its release. The effects of ethanolamine-O-sulfate (EOS), a gamma-aminobutyric acid (GABA)-transaminase blocker, on GABAergic postsynaptic and presynaptic inhibitory neurotransmission were examined in the crayfish opener neuromuscular synapses. 2. Intracellular recordings of evoked excitatory (EPSPs) and inhibitory postsynaptic potentials (IPSPs) as well as loose macropatch clamp measurements of excitatory (EPSCs) and inhibitory postsynaptic currents (IPSCs) were used to evaluate the effects of the drug, which was applied exclusively to the nerve bundle. 3. Under normal conditions, a stimulus train to the inhibitor before the excitor stimulation elicited two phases of inhibition: 1) a large reduction in EPSP amplitude associated with a decrease in its time constant of decay (tau D) at time intervals of 0-15 ms and 2) a moderate decrease in EPSP amplitude with a small change in EPSP tau D at intervals of 15-90 ms. EOS treatment selectively increased the inhibition of phase 2. 4. The muscle membrane electrical parameters and the existing postsynaptic tonic release of GABA were not affected by the drug. 5. EOS did not alter the IPSP's parameters such as amplitude, reversal potential, and conductance. 6. Quantal analysis of single IPSCs revealed no significant changes in the statistical parameters such as quantum size (q), quantal content (m), number of active zones (n), or probability of release (p). 7. Quantal analysis of EPSCs, released after interaction with the inhibitor, did exhibit a large reduction in m without any effect on q. 8. These results demonstrate that EOS has a specific and differential effect on neural transmission in two synapses of the same axon: it increases presynaptic inhibition without significant effect on the postsynaptic inhibitory mechanism.

Limits of quantal analysis reliability: quantal and unimodal constraints and setting of confidence intervals for quantal size

An accurate objective method for determining the reliability of estimates of quantal size ( Q) at central synapses was developed. To do this, distributions of amplitudes of postsynaptic responses were simulated by convolving a number of discrete amplitudes separated by equal increments Q with gaussian noise, after which the value of Q was estimated by the maximum likelihood method under different constraints on the discrete distribution. It was shown that the likelihood function (LF) had several local maxima under the quantal constraint, and, if the value of the ratio between Q and the standard deviation of the noise (σ) was less than 3, the global maximum of the LF corresponded to a biased estimate of Q lying in a range of values less than 1.5σ. The best estimates of Q were obtained when unimodal discrete distributions of amplitudes resulting from the maximum likelihood method were selected. However, this method also gave biased estimates when Q/ σ was less than 1.5–2.3. The limit of reliability depended on the number of discrete components and the sample size. To calculate confidence intervals for the quantal size, different numbers and weights of components were used to simulate amplitude histograms with different values of Q/ σ. Three data sets were used to illustrate the procedure.

Occurrence and three-dimensional structure of multiple synapses between individual radiatum axons and their target pyramidal cells in hippocampal area CA1

Recent physiological work has used quantal analysis to investigate the properties of synaptic transmission and long-term potentiation in hippocampal area CA1. These analyses have revealed changes in the strength of excitatory post-synaptic responses following long-term potentiation that could be mediated by cellular mechanisms in the presynaptic element, in the postsynaptic element, or in both elements. In these studies, either minimal stimulation, presumably involving a single presynaptic axon, or recordings from pairs of CA3 and CA1 cells have been used. Interpretation of these quantal analyses requires knowledge about whether single or multiple synapses occur between the presynaptic axon and its target CA1 pyramidal cells. Here, light and serial electron microscopy was used to begin to examine this question and a related question concerning the ultrastructure of spines on multiple-synapse boutons. Light microscopic analyses of Golgi preparations revealed that about 20% of the axons occurring in stratum radiatum come into close apposition with two to four different dendrites of a target CA1 cell. An "apposition" was defined as a point where the axons and dendrites crossed in the same focal plane and therefore were sufficiently close to allow a dendritic spine to reach the axon and possibly establish a synaptic contact. An additional 4% of the axons wound back and forth across individual dendrites, possibly forming multiple synapses closely spaced along the dendrites. Serial electron microscopy revealed that 24% of the individual axonal boutons in stratum radiatum make synapses with multiple dendritic spines arising from either the same or different dendritic segments. Two adjacent boutons of the same axon could also be found to synapse with different spines of the same dendrite. Together with the light microscopic analysis, these observations suggest that multiple synapses occur between single axons in stratum radiatum and their target CA1 cells, and that at least some of these synapses may occur at different electronic distances. If these multiple synapses have different physiological strengths, then they may obscure or smooth peaks in the frequency histograms that are used for quantal analyses. A three-dimensional analysis was done to compare the dimensions of pairs of dendritic spines synapsing with individual axonal boutons. When the pairs of spines associated with a single bouton arose from different dendrites, at least some of which were likely to have come from different cells, the differences between their volumes and the areas of the postsynaptic densities were on average 100% and ranged up to 650%.(ABSTRACT TRUNCATED AT 400 WORDS)

A role for postsynaptic neurons in determining presynaptic release properties in the cricket CNS: evidence for retrograde control of facilitation

Intracellular recording sin the cricket cercal system show that the synaptic terminals of a single sensory neuron can facilitate at one target, the medial giant interneuron (MGI), and simultaneously depress at another target, interneuron 10-3. A quantal analysis of transmission at these synapses demonstrates that facilitation and depression are properties of the presynaptic cell. For facilitating synapses contacting MGI, the mean quantal content (m), determined from the probability of the failures, increases for the second EPSP, while the quantal size (q) remains constant. Similarly, an analysis of depression for those synapses contacting 10-3 supports a presynaptic mechanism for depression. Since facilitation and depression are presynaptic and their expression at the synapses of a single, identified sensory neuron are correlated with the target interneuron, we conclude that these properties are regulated locally, at the synapse, possibly by an interaction with the postsynaptic cell.

On the quantal analysis of hippocampal long-term potentiation and related phenomena of synaptic plasticity

On the quantal analysis of hippocampal long-term potentiation and related phenomena of synaptic plasticity

Synaptic Plasticity in the Cerebral Ganglion of Aplysia

The A-B neuron synapses in the cerebral ganglion of Aplysia exhibit two prominent forms of activity-dependent plasticity. Stimulating individual presynaptic A neurons at low frequencies (0.002-5 Hz) causes synaptic depression of EPSPs and EPSCs in postsynaptic B neurons, while tetanizing A neurons with 4,500 ms trains of 35 ms pulses at 20 Hz evokes a long-lasting (~25 min) increase in EPSP amplitudes. Due to its slow kinetics, we have called this latter plasticity slow developing potentiation (SDP). Both depression and SDP are neuron-specific. Several lines of evidence support the hypothesis that SDP has a presynaptic locus. SDP can be induced while voltage clamping the postsynaptic neuron. There are no changes in either input resistance or the steady-state I-V curve of B neurons during SDP. SDP does not require depolarization and spiking by the postsynaptic neuron. Pairing pre- and postsynaptic tetanization fails to increase SDP. Additionally, the reversal potential of the control and potentiated EPSCs are essentially the same (+ 11-12 mV). In contrast, there is a significant reduction in total outward current in the presynaptic A neurons following the tetanization. However, SDP does not appear to be due to the inactivation of a steady-state K+ current. SDP may be in part mediated by PKC. PKC activators enhance SDP, while injecting the peptide inhibitor PKC19-36 blocks it. Both Ca2+ entry, antagonized by L-channel blockers and ryanodine-sensitive release of Ca2+ from internal stores appear to contribute to SDP. Using quantal analysis, three independent measures indicate that SDP is due to increased quantal content. All these changes are consistent with an SDP requiring an increase in intracellular Ca2+, leading to increased transmitter release and a primary, if not exclusive, presynaptic locus for the observed synaptic plasticity.

Quantal analysis of modulating action of adenosine on the mossy fiber synapse in hippocampal slices.

Although adenosine has been considered to depress release of neurotransmitter in central synapses, evidence for this notion is circumstantial. To obtain more direct and quantitative evidence, the suppressing action of adenosine on transmission through the mossy fiber synapse was examined by a quantal analysis in thin transverse sections of the guinea pig hippocampus. Adenosine suppressed excitatory postsynaptic potentials (EPSPs) induced in CA3 neurons by activation of single mossy fibers to 57 +/- 19% at 10 microM (6 neurons). The input resistance of the postsynaptic neurons was reduced to 84 +/- 5%. The suppression of the unitary EPSPs was accompanied by a reduction of the mean quantal content (m) to 51 +/- 13% with no significant decrease in mean quantal amplitude (q). These findings indicate that adenosine at 10 microM suppresses transmission through mossy fiber synapses mainly by depressing release of transmitter. This study provides direct evidence for the presynaptic action of adenosine on central synapses for the first time.