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D S Melkonian

Publications and source records attributed to D S Melkonian.

10 recordsLinked to original sources

Novel approach to a quantitative treatment of the quantal transmitter release at the frog neuromuscular junction.

To explain the discrepancy between estimates of parameters of quantal transmitter release received by different techniques the paper postulates a novel concept for quanta mobilization, which assumes that a quantum emitted by a vesicle transiently acquires a transition state in which it is immediately available for release. The working particle model is formulated in terms of probabilities of inter-state quanta transitions. The parameters of the model are determined by fitting solutions to the experimental curves representing short-term changes of synaptic efficacy at the frog neuromuscular junction as well as taking into account the morphologically estimated number of releasable vesicles. The value of the model is demonstrated by successful prediction of the estimates of the parameters of the quantal transmitter release suggested by evidence received from different lines of research.

Animals↗

Stochastic particle formulation of the vesicle hypothesis. Relevance to short-term phenomena.

Based on the vesicle hypothesis, the modes of elementary quantum-vesicle interactions have been formulated in terms of probabilities of induced and spontaneous interstate quanta transitions and generalized within the framework of the previously developed theory of the double barrier synapse. Among the three allowed states for a quantum, the transition state is a novel formulation for the fraction of immediately available quanta governed by both vesicle and presynaptic membranes. The parameters of the model were determined by fitting solutions to the experimental curves representing effects of single pulse and short train activation on transmitter release at the frog neuromuscular junction. Qualitative differences in particle physics of transmitter release found under low quantal outputs on one hand and normal transmission on the other allowed the formulation of the uncertainty hypothesis and the quantum condition of synaptic homeostasis.

Computer Simulation↗

Direct evidence for the synaptic resonance phenomenon.

Via the parameter optimization method, well documented in the literature, data on the facilitated release of acetylcholine from the preganglionic nerve terminals during short trains of impulses have been quantitatively generalized within the framework of the previously developed theory of the double barrier synapse. This allowed unique transformation of the set of discrete measurements of facilitated transmitter release into continuous dependencies of facilitation on time and frequency and, subsequently, into the resonant curves having very readily interpreted computational meaning. Thus direct evidence is produced that an overall effect of facilitory action of presynaptic stimulation does indeed reflect resonant properties of the terminal in a form of the previously predicted synaptic resonance phenomenon.

Acetylcholine↗

Transient analysis of a chemical synaptic transmission.

The statistical dynamics of an impulse induced quanta turnover is studied by means of a nonstationary stochastic model--double barrier synapse--resulting from a previously developed mathematical theory of chemical synaptic transmission. An essential aspect of nonstationarities of the model is that the interpool quanta transfers follow binomial distribution at impulse arrival time, while in the absence of stimulation they obey Yule-Furry statistics. Under a variety of conditions, corresponding to those in actual experiments, the transient behaviour of the model is simulated and analysed in detail. As a result, the quantitative description of immediate and delayed components of synaptic action is introduced. If simulations of quantal fluctuations are performed numerically, then for the treatment of dynamic regularities, besides numerical procedures, an analytical method of envelopes is developed. It is supported by the theorems which reduce behaviour of the double-barrier synapse to the super-position of simpler solutions for single-barrier systems. With short-term facilitation quantitative analysis and simulations, the synaptic resonance phenomenon is theoretically predicted: different resonant frequencies are found at different levels of facilitation. The importance of this phenomenon treated as a clue to the information processing capabilities of a chemical synapse is discussed.

Animals↗

Pattern dependent form of synaptic modification and its quantal origins.

Presynaptic mechanisms of post-activation changes of synaptic efficacy have been quantitatively reconstructed via computer simulations with the previously suggested double-barrier quantal model of a chemical synapse. Successful in predicting the global changes in synaptic efficacy during and after short trains of presynaptic impulses, computer reconstructions have revealed in the post-activation period the stimulus dependent form of synapse modification from short-term to longer-term plasticity. An analysis of the quantal origins of the phenomenon suggests semantic or S-pattern as the trigger of the phenomenon. The property of a semantic pattern to modify synaptic plasticity is presented in the form of the rule of S-pattern dependent synaptic modification or S-modification.

Kinetics↗

Double barrier quantal model of neurotransmitter release.

As an extension of the particle concept in the quantitative descriptive of an entire neurotransmitter population, which participates in quanta release from the terminal, an improved system of quantal postulates is suggested. An essential aspect of the corresponding double barrier quantal model is its nonstationarity, resulting from combined application of binomial and Yule-Furry statistics. Results of the computer simulations show that the model combines enough ingredients to reproduce, with fair accuracy, the main characteristic features of short-term changes of synaptic efficacy under the different conditions of presynaptic stimulation. With quantitative analysis and simulation of short-term facilitation, the synaptic resonance phenomenon is theoretically predicted: different resonant frequencies are found at different levels of facilitation.

Computer Simulation↗

[Glial origin of negative shifts in the surface potential of the brain upon tetanic stimulation: microelectrode study and mathematical analysis].

It is shown in experiments on anesthetized cats that negative shift of the cortical surface potential evoked by its tetanic stimulation is similar in form and time course to the depolarization of glial cells. On the contrary, hyperpolarizing shifts of neuronal membrane potential are dissimilar in form and time course to the negative shift of the cortical surface potential. A conclusion is made that the contribution of neuronal hyperpolarization to the surface-negative shift of the potential can distinctly be seen only at the beginning of tetanization--in the first 200-300 ms; negative shift of the cortical surface potential is mainly produced by depolarization of glial cells.

Animals↗

Simulation of learning processes in neuronal networks of the cerebellum.

A dynamic model of learning that is based on the specific neuronal system of the cerebellum, including some of its structural-functional peculiarities, is proposed. It allows to simulate modification processes of the parallel fiber synapse that influences the Purkinje cell. regularities of synaptic modifications are obtained by extrapolating well-known experimental data bout changes of synaptic efficiency as resulting from release, refilling and mobilization of the mediator. It is shown that a mathematical description of synaptic processes corresponds to experimental data on the changes of synaptic efficiency under rhythmical stimulation and gives objective quantitative estimates for long-term (refilling of the mediator) and short-term (mobilization of the mediator) effects which are caused by presynaptic stimulation. Computer simulations have been conducted to investigate the characteristics of learning for different values of the following parameters: intensity of unconditioned stimulus (US, activity of the climbing fibre), intensity of conditioned stimulus (CS, activity of the parallel fibre), temporal shift between US and CS, temporal interval between reinforcements. It is shown that the temporal shift between CS and US is one of the major factors that influence the learning procedures. Analysis of the data obtained shows that the model enables us to simulate the main regularities of establishment and extinction of conditioned reflexes.

Animals↗

[Glial origin of the slow negative potential of the direct cortical response: microelectrode study and mathematical analysis].

Slow negative potential of a direct cortical response is similar in configuration, time-course and reaction to repeated stimuli to depolarization of the cortical glial cells and differs from IPSP of the cortical neurons. According to data of digital spectral (frequency) analysis, slow negative potential is based on the glial component formed by summing up the constituents, which coincide with glial depolarization within a constant factor. The neuronal component, whose contribution is comparatively much smaller, is an indirect result of IPSP.

Animals↗