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Buffering by Transporters Can Spare Geometric Hindrance in Controlling Glutamate Escape

Savtchenko, LP; Zheng, K; Rusakov, DA; (2021) Buffering by Transporters Can Spare Geometric Hindrance in Controlling Glutamate Escape. Frontiers in Cellular Neuroscience , 15 , Article 707813. 10.3389/fncel.2021.707813. Green open access

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Abstract

The surface of astrocyte processes that often surround excitatory synapses is packed with high-affinity glutamate transporters, largely preventing extrasynaptic glutamate escape. The shape and prevalence of perisynaptic astroglia vary among brain regions, in some cases providing a complete isolation of synaptic connections from the surrounding tissue. The perception has been that the geometry of perisynaptic environment is therefore essential to preventing extrasynaptic glutamate escape. To understand to what degree this notion holds, we modelled brain neuropil as a space filled with a scatter of randomly sized, overlapping spheres representing randomly shaped cellular elements and intercellular lumen. Simulating release and diffusion of glutamate molecules inside the interstitial gaps in this medium showed that high-affinity transporters would efficiently constrain extrasynaptic spread of glutamate even when diffusion passages are relatively open. We thus estimate that, in the hippocampal or cerebellar neuropil, the bulk of glutamate released by a synaptic vesicle is rapidly bound by transporters (or high-affinity target receptors) mainly in close proximity of the synaptic cleft, whether or not certain physiological or pathological events change local tissue geometry.

Type: Article
Title: Buffering by Transporters Can Spare Geometric Hindrance in Controlling Glutamate Escape
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fncel.2021.707813
Publisher version: https://doi.org/10.3389/fncel.2021.707813
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: excitatory synapse, glutamate, glutamate spillover, glutamate transporters, astrocyte, perisynaptic astroglial processes, synaptic environment
UCL classification: UCL
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/10133207
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