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Exocytotic dynamics and calcium cooperativity effects in the calyx of Held synapse: a modelling study

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Abstract

A stochastic computational approach to the study of secretory processes at the calyx of Held synapse is presented in this paper. The calyx of Held is a giant synapse located in the brainstem which is widely used for experimental recording of neurotransmitter release. We focus on the study of the exocytotic dynamics for a pool of readily releasable vesicles using a Monte Carlo simulation scheme that includes models for the P-type calcium channels, the kinetic reactions of endogenous and exogenous (mobile) buffers, the kinetic reactions for the secretory vesicles, as well as the microscopic diffusion of mobile buffers and calcium ions. The simulations are performed in a 3-D orthogonal grid which approximates a cylindrical domain representing an active zone of the presynaptic terminal of the calyx. For this domain, we quantify the release rates related to calcium currents in response to depolarizing voltage pulses. The influence on simulated pulse/action potential depolarization protocols of the kinetic scheme for the calcium sensor of vesicles and the geometry of calcium channels for the kinetic cooperativity for release, is analyzed at a microdomain level. Among other aspects, our results suggest that the spatial organization of Ca 2 +  channels could have measurable effects in the kinetic cooperativity which could reflect developing changes in the calyx of Held synapse.

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Acknowledgements

The authors acknowledge the three anonymous referees for useful comments and suggestions. The authors also acknowledge useful discussions with J. Segura (U. Cantabria) and financial support from I-MATH project C3-0136. V. González-Vélez thanks CONACyT for financial support through her PhD scholarship.

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Authors and Affiliations

  1. Depto. de Matemática Aplicada y Ciencias de la Computación, Universidad de Cantabria, 39005, Santander, Spain

    Amparo Gil

  2. Area de Química Aplicada, Universidad Autónoma Metropolitana Azcapotzalco, 02200, México D.F., Mexico

    Virginia González-Vélez

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  1. Amparo Gil
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Correspondence to Amparo Gil.

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Action Editor: Upinder Singh Bhalla

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Gil, A., González-Vélez, V. Exocytotic dynamics and calcium cooperativity effects in the calyx of Held synapse: a modelling study. J Comput Neurosci 28, 65–76 (2010). https://doi.org/10.1007/s10827-009-0187-x

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