title: Time-coded neurotransmitter release at excitatory and inhibitory synapses.
abstract: Communication between neurons at chemical synapses is regulated by hundreds of different proteins that control the release of neurotransmitter that is packaged in vesicles, transported to an active zone, and released when an input spike occurs. Neurotransmitter can also be released asynchronously, that is, after a delay following the spike, or spontaneously in the absence of a stimulus. The mechanisms underlying asynchronous and spontaneous neurotransmitter release remain elusive. Here, we describe a model of the exocytotic cycle of vesicles at excitatory and inhibitory synapses that accounts for all modes of vesicle release as well as short-term synaptic plasticity (STSP). For asynchronous release, the model predicts a delayed inertial protein unbinding associated with the SNARE complex assembly immediately after vesicle priming. Experiments are proposed to test the model's molecular predictions for differential exocytosis. The simplicity of the model will also facilitate large-scale simulations of neural circuits.
authors: School of Computing and Mathematics, Plymouth University, Plymouth PL4 8AA, United Kingdom;
authors: Serafim
authors: S
authors: Rodrigues
authors: Inria Sophia Antipolis Mediterranee Research Centre, MathNeuro Team, 06902 Sophia Antipolis cedex, France;
authors: Mathieu
authors: M
authors: Desroches
authors: Inria Sophia Antipolis Mediterranee Research Centre, MathNeuro Team, 06902 Sophia Antipolis cedex, France;
authors: Martin
authors: M
authors: Krupa
authors: Biocruces Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Bizkaia, Spain; Departamento de Biologia Celular e Histologia, University of the Basque Country, 48940 Leioa, Bizkaia, Spain;
authors: Jesus M
authors: JM
authors: Cortes
authors: The Computational Neurobiology Laboratory, Salk Institute, La Jolla, CA 92037; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037; Division of Biological Science, University of California, San Diego, La Jolla, CA 92093; terry@salk.edu.
authors: Terrence J
authors: TJ
authors: Sejnowski
authors: UCL School of Pharmacy, Department of Pharmacology, University College London, London WC1N 1AX, United Kingdom.
authors: Afia B
authors: AB
authors: Ali
mesh_terms: D000818:Animals; D005089:Exocytosis / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents
keywords: SM complex; SNARE complex; asynchronous neurotransmitter release; exocytotic-endocytotic cycle; short-term synaptic plasticity