%0 Journal Article %T A first-passage approach to diffusion-influenced reversible binding and its insights into nanoscale signaling at the presynapse %+ Dynamique des synapses et des circuits neuronaux - Synapse and circuit dynamics %+ Ecole doctorale Cerveau Cognition et Comportement [Paris] (ED 158 - 3C) %+ Laboratoire de physique de la matière condensée (LPMC) %A Reva, Maria %A Digregorio, David %A Grebenkov, Denis, S %Z This study was supported by the Centre National de la Recherche Scientifique, Fondation pour la Recherche Medicale (Equipe FRM), Agence Nationale de la Recherche (ANR-2010-BLANC-1411, ANR-13-BSV4-0016, ANR-17-CE16-0019, and ANR-17-CE16-0026), and Ile de France (Domaine d’Interet Majeur (DIM) MALINF: DIM120121). M.R. was supported by the Pasteur Paris University (PPU) doctoral program. The laboratory of D.D. is a member of the Bio-Psy Laboratory of Excellence. We would like to thank Yukihiro Nakamura for sharing simulated calcium transients, Jean-Baptiste Masson and Nelson Rebola for the comments on the manuscript and discussions. %< avec comité de lecture %@ 2045-2322 %J Scientific Reports %I Nature Publishing Group %V 11 %N 1 %P 5377 %8 2021-12 %D 2021 %R 10.1038/s41598-021-84340-4 %M 33686123 %Z Cognitive scienceJournal articles %X Synaptic transmission between neurons is governed by a cascade of stochastic calcium ion reaction-diffusion events within nerve terminals leading to vesicular release of neurotransmitter. Since experimental measurements of such systems are challenging due to their nanometer and sub-millisecond scale, numerical simulations remain the principal tool for studying calcium-dependent neurotransmitter release driven by electrical impulses, despite the limitations of time-consuming calculations. In this paper, we develop an analytical solution to rapidly explore dynamical stochastic reaction-diffusion problems based on first-passage times. This is the first analytical model that accounts simultaneously for relevant statistical features of calcium ion diffusion, buffering, and its binding/unbinding reaction with a calcium sensor for synaptic vesicle fusion. In particular, unbinding kinetics are shown to have a major impact on submillisecond sensor occupancy probability and therefore cannot be neglected. Using Monte Carlo simulations we validated our analytical solution for instantaneous calcium influx and that through voltage-gated calcium channels. We present a fast and rigorous analytical tool that permits a systematic exploration of the influence of various biophysical parameters on molecular interactions within cells, and which can serve as a building block for more general cell signaling simulators. %G English %2 https://pasteur.hal.science/pasteur-03166835/document %2 https://pasteur.hal.science/pasteur-03166835/file/Reva_et_al-2021-Scientific_Reports.pdf %L pasteur-03166835 %U https://pasteur.hal.science/pasteur-03166835 %~ PASTEUR %~ X %~ CNRS %~ X-PMC %~ X-DEP %~ X-DEP-PHYS %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ IP_PARIS %~ IP_PARIS_COPIE %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ SU-TI %~ ANR %~ ALLIANCE-SU %~ FRM %~ SYN-CIR-DY %~ PASTEUR_UMR3571