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Physical determinants of vesicle mobility and supply at a central synapse

Rothman, JS; Kocsis, L; Herzog, E; Nusser, Z; Silver, RA; (2016) Physical determinants of vesicle mobility and supply at a central synapse. eLIFE , 5 , Article e15133. 10.7554/eLife.15133. Green open access

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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 VGLUT1Venus 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.

Type: Article
Title: Physical determinants of vesicle mobility and supply at a central synapse
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.15133
Publisher version: http://doi.org/10.7554/eLife.15133
Language: English
Additional information: Copyright Rothman et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biology, Life Sciences & Biomedicine - Other Topics, HARD-SPHERE SUSPENSIONS, MOTOR-NERVE TERMINALS, TIME SELF-DIFFUSION, IN-VIVO, RIBBON SYNAPSE, HIPPOCAMPAL SYNAPSES, VESICULAR RELEASE, AUDITORY SYNAPSE, BROWNIAN-MOTION, AMPA RECEPTORS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1508949
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