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Bayesian analysis of the kinetics of quantal transmitter secretion at the neuromuscular junction

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Abstract

The timing of transmitter release from nerve endings is considered nowadays as one of the factors determining the plasticity and efficacy of synaptic transmission. In the neuromuscular junction, the moments of release of individual acetylcholine quanta are related to the synaptic delays of uniquantal endplate currents recorded under conditions of lowered extracellular calcium. Using Bayesian modelling, we performed a statistical analysis of synaptic delays in mouse neuromuscular junction with different patterns of rhythmic nerve stimulation and when the entry of calcium ions into the nerve terminal was modified. We have obtained a statistical model of the release timing which is represented as the summation of two independent statistical distributions. The first of these is the exponentially modified Gaussian distribution. The mixture of normal and exponential components in this distribution can be interpreted as a two-stage mechanism of early and late periods of phasic synchronous secretion. The parameters of this distribution depend on both the stimulation frequency of the motor nerve and the calcium ions’ entry conditions. The second distribution was modelled as quasi-uniform, with parameters independent of nerve stimulation frequency and calcium entry. Two different probability density functions for the distribution of synaptic delays suggest at least two independent processes controlling the time course of secretion, one of them potentially involving two stages. The relative contribution of these processes to the total number of mediator quanta released depends differently on the motor nerve stimulation pattern and on calcium ion entry into nerve endings.

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Abbreviations

TCS:

Time course of secretion

EPC:

Endplate current

EMG:

Exponentially modified Gaussian

[Са2+]out :

Extracellular calcium concentration

[Mg2+]out :

Extracellular magnesium concentration

4-AP:

4-aminopyridine

QU:

Quasi-uniform process

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Acknowledgments

Supported by the Russian Government’s Program for Competitive Growth of Kazan Federal University and was also supported by a grant of President of Russian Federation “Leading Scientific School” and a grants from the Russian Foundation for Basic Research (13-04-00886 for DS; 14-04-00987 for IK and EN, 14-04-00790 for AS, 15-04-02983 for VKh and EB).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Kazan Federal University, Kremlevskaya St. 18, Kazan, 420008, Russia

    Anatoly Saveliev, Venera Khuzakhmetova, Dmitry Samigullin, Andrey Skorinkin, Irina Kovyazina, Eugeny Nikolsky & Ellya Bukharaeva

  2. Laboratory of the Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, P.O. Box 30, Kazan, 420111, Russia

    Venera Khuzakhmetova, Dmitry Samigullin, Andrey Skorinkin, Irina Kovyazina, Eugeny Nikolsky & Ellya Bukharaeva

  3. Kazan National Research Technical University named after A. N. Tupolev, K. Marx St. 10, Kazan, 420111, Russia

    Dmitry Samigullin

  4. Kazan State Medical University, Butlerov St. 49, Kazan, 420012, Russia

    Eugeny Nikolsky

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  1. Anatoly Saveliev
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  2. Venera Khuzakhmetova
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Correspondence to Ellya Bukharaeva.

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Saveliev, A., Khuzakhmetova, V., Samigullin, D. et al. Bayesian analysis of the kinetics of quantal transmitter secretion at the neuromuscular junction. J Comput Neurosci 39, 119–129 (2015). https://doi.org/10.1007/s10827-015-0567-3

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