Modelling vesicular release at hippocampal synapses

• Published in: PLoS computational biology Vol. 6; no. 11; p. e1000983
• Main Authors: Nadkarni, Suhita, Bartol, Thomas M, Sejnowski, Terrence J, Levine, Herbert
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-11-2010; Public Library of Science (PLoS)
• Subjects: Biophysics/Biomacromolecule-Ligand Interactions; Biophysics/Cell Signaling and Trafficking Structures; Biophysics/Theory and Simulation; CA1 Region, Hippocampal; CA3 Region, Hippocampal; Calcium; Calcium - metabolism; Cell Biology/Cell Signaling; Computational biology; Computational Biology/Computational Neuroscience; Computational Biology/Signaling Networks; Computer Simulation; Diffusion; Exocytosis - physiology; Experiments; Hippocampus (Brain); Models, Neurological; Monte Carlo Method; Neural transmission; Neuronal Plasticity - physiology; Neuroscience/Neuronal and Glial Cell Biology; Neuroscience/Neuronal Signaling Mechanisms; Neuroscience/Theoretical Neuroscience; Physiological aspects; Proteins; Reproducibility of Results; Stochastic Processes; Studies; Synapses - chemistry; Synaptic Transmission - physiology; Synaptic Vesicles - chemistry; United States; Reproducibility of Results; Calcium; CA3 Region, Hippocampal; Exocytosis; Synaptic Transmission; Synaptic Vesicles; Stochastic Processes; Neuronal Plasticity; Computer Simulation; CA1 Region, Hippocampal; Models, Neurological; Monte Carlo Method; Synapses
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1000983

We study local calcium dynamics leading to a vesicle fusion in a stochastic, and spatially explicit, biophysical model of the CA3-CA1 presynaptic bouton. The kinetic model for vesicle release has two calcium sensors, a sensor for fast synchronous release that lasts a few tens of milliseconds and a separate sensor for slow asynchronous release that lasts a few hundred milliseconds. A wide range of data can be accounted for consistently only when a refractory period lasting a few milliseconds between releases is included. The inclusion of a second sensor for asynchronous release with a slow unbinding site, and thereby a long memory, affects short-term plasticity by facilitating release. Our simulations also reveal a third time scale of vesicle release that is correlated with the stimulus and is distinct from the fast and the slow releases. In these detailed Monte Carlo simulations all three time scales of vesicle release are insensitive to the spatial details of the synaptic ultrastructure. Furthermore, our simulations allow us to identify features of synaptic transmission that are universal and those that are modulated by structure.