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Frequency-Dependent Engagement of Synaptic Vesicle Pools in the Mice Motor Nerve Terminals

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Nerve terminals contain numerous synaptic vesicles (SVs) whose exo-endocytic cycling maintains neurotransmitter release. SVs may have different properties, thereby constituting separate pools. However, behavior of SV pools remains elusive in many synapses. To fill this gap, we studied the functioning of SV pools at both low- and higher-frequency stimulations utilizing microelectrode recording and dual-labeling of SVs with FM-dyes at the mice motor nerve terminals. It was found that higher-frequency stimulation caused exocytosis of different kinds of SVs. One type of SVs contributed to exocytosis exclusively at intense activities and their exocytotic rate was depended on the order in which these SVs were recovered by endocytosis. Another type of SVs can sustain the release in response to both low- and higher-frequency stimulations, but increasing activity did not lead to enhanced exocytotic rate of these SVs. In addition, depression of neurotransmitter release induced by 20 Hz stimulation occurred independent on previous episode of 10 Hz activity. We suggest that during prolonged stimulation at least two SV pools can operate. One termed “house-keeping” that would be active at different frequencies and the other termed “plug-in” that would respond to increasing activity.

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All mentioned data are represented in the main manuscript figures and supplementary figures. Other additional data will be made available on reasonable request.



End-plate potential


Neuromuscular junction


Synaptic vesicle


Ready releasable pool


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We thank Dr. A.V. Zakharov (Kazan Federal University) for discussion of the work and Dr. Nicole El-Darzi (Case Western Reserve University) for carefully reading the manuscript and helpful comments. AMP and ANT were supported by the government assignment for FRC Kazan Scientific Center of RAS.


This study was supported by Russian Science Foundation Grant #21-14-00044,

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Authors and Affiliations



C.R.G. and A.N.T. produced and analyzed data. All authors interpreted results of experiments. A.M.P. supervised the research and wrote the manuscript. All the authors approved the final version of the manuscript.

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Correspondence to Alexey M. Petrov.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors consent to publish the article.

Ethical Approval

The present study was conducted in compliance with the NIH Guide for the Care and Use of Laboratory Animals. The experimental protocol met the requirements of the EU Directive 2010/63/EU and European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Council of Europe No 123, Strasbourg, 1985). The protocol of experiments was approved by the Local Bioethics Committees (Kazan Medical University; Protocol #5/May 27, 2014).

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There is not applicable. This manuscript does not contain any studies with human participants.

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Gafurova, C.R., Tsentsevitsky, A.N. & Petrov, A.M. Frequency-Dependent Engagement of Synaptic Vesicle Pools in the Mice Motor Nerve Terminals. Cell Mol Neurobiol 43, 729–739 (2023).

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