title: Physical determinants of vesicle mobility and supply at a central synapse.
abstract: Encoding continuous sensory variables requires sustained synaptic signalling. At several sensory synapses, rapid vesicle supply is achieved via highly mobile vesicles and specialized ribbon structures, but how this is achieved at central synapses without ribbons is unclear. Here we examine vesicle mobility at excitatory cerebellar mossy fibre synapses which sustain transmission over a broad frequency bandwidth. Fluorescent recovery after photobleaching in slices from VGLUT1(Venus) knock-in mice reveal 75% of VGLUT1-containing vesicles have a high mobility, comparable to that at ribbon synapses. Experimentally constrained models establish hydrodynamic interactions and vesicle collisions are major determinants of vesicle mobility in crowded presynaptic terminals. Moreover, models incorporating 3D reconstructions of vesicle clouds near active zones (AZs) predict the measured releasable pool size and replenishment rate from the reserve pool. They also show that while vesicle reloading at AZs is not diffusion-limited at the onset of release, diffusion limits vesicle reloading during sustained high-frequency signalling.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
authors.forename: Jason Seth
authors.identifier: 0000-0003-3036-2291
authors.initials: JS
authors.lastname: Rothman
authors.affiliation: Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kocsis
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.|Team Synapse in Cognition, Interdisciplinary Institute for Neuroscience, Université de Bordeaux, UMR 5297, F-33000, Bordeaux, France.
authors.forename: Etienne
authors.identifier: 0000-0002-0058-6959
authors.initials: E
authors.lastname: Herzog
authors.affiliation: Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Zoltan
authors.identifier: 0000-0001-7004-4111
authors.initials: Z
authors.lastname: Nusser
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
authors.forename: Robin Angus
authors.identifier: 0000-0002-5480-6638
authors.initials: RA
authors.lastname: Silver
mesh_terms: D000818:Animals; D051379:Mice; D009038:Motion; D009412:Nerve Fibers / Q000502:physiology*; D061848:Optical Imaging; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*
keywords: active zone; diffusion; hydrodynamic interactions; mouse; neuroscience; synaptic transmission; vesicle mobility; vesicle supply