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Biomedical subjects

A E Dityatev

Publications and source records attributed to A E Dityatev.

5 recordsLinked to original sources

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.

Animals

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 (sigma) 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 1.5 sigma. 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/sigma 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/sigma. Three data sets were used to illustrate the procedure.

Animals

Modeling of the quantal release at interneuronal synapses: analysis of permissible values of model moments.

A theoretical study of effects of the different factors on fluctuation of post-synaptic potential (PSP) amplitudes was undertaken, using computation of regions of permissible values (RPV) of the ratio between the variance and the mean number of the quanta released (R1) and the ratio between the third moment and the variance (R2). The RPVs of these indexes for the binomial model were compared with regions determined for a number of models incorporating several factors. It has been shown that the involvement of temporal non-uniformity of transmitter release probability, decremental spreading of potentials along dendrites, and failure of spike propagation give the values of skewness index R2 less, compared to the binomial model. Simultaneously, a number of other factors, especially spatial non-uniformity of release probabilities in single release sites, would give amplitude histograms with high positive values of the index. The values of R1 and R2, calculated for 21 samples of sensorimotor EPSP amplitudes, were biased from RPV of these parameters constructed for the binomial model. The scattergram of R1 and R2 can be explained by the presence of two kinds of contacts which release quantum with different probabilities. The same was true for the beta-model based on the assumption that probabilities of quantal release are a sample of values of random variable that has beta-distribution. From analysis of the distribution of individual release probabilities, obtained from evaluation of beta-model parameters, is concluded that a greater part of boutons in the sensorimotor synapses release transmitter with very low probabilities, there being, however, a few boutons with probabilities close to 1.

Animals

Physicochemical properties of signal receptor domains as the basis for sequence comparison.

1. An algorithm of sequence comparison based on average bulkiness of amino acids in protein domains and not requiring sequence alignment is described. 2. A complete evolutionary tree of the signal receptor proteins is built. The STE2 proteins are shown to belong to this family. 3. Factorial analysis of average bulkiness makes it possible to discriminate functional and intraspecies differences between proteins.

Algorithms

Ligand-receptor interactions. Multidimensional mathematical method of analysis.

The paper embraces information about the character of interaction between pharmacologically active ligands and 11 G-protein-dependent receptors of neurotransmitters. The data are analyzed by the methods of correlation and cluster analyses and of main components. An essential pharmacological affinity is revealed to exist between the receptors which regulate an inhibitory link of the adenylate cyclase system and receptors which activate Ca(2+)-mobilizing polyphosphoinositide system of secondary transmitters. Receptors which activate adenylate cyclase are rather different pharmacologically from two previous groups. Interrelation between the structure and physico-chemical properties of binding sites on receptors and efficiency of their interaction with ligand is discussed.

Adenylyl Cyclases