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Extracellular glutamate and GABA transients at the transition from interictal spiking to seizures

Shimoda, Yoshiteru; Leite, Marco; Graham, Robert T; Marvin, Jonathan S; Hasseman, Jeremy; Kolb, Ilya; Looger, Loren L; ... Kullmann, Dimitri M; + view all (2024) Extracellular glutamate and GABA transients at the transition from interictal spiking to seizures. Brain , 147 (3) , Article awad336. 10.1093/brain/awad336. Green open access

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Abstract

Focal epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood. We used fluorescent glutamate and GABA sensors in an awake rodent model of neocortical seizures to resolve the spatiotemporal evolution of both neurotransmitters in the extracellular space. Interictal spikes were accompanied by brief glutamate transients which were maximal at the initiation site and rapidly propagated centrifugally. GABA transients lasted longer than glutamate transients and were maximal ∼1.5 mm from the focus where they propagated centripetally. Prior to seizure initiation GABA transients were attenuated, whilst glutamate transients increased, consistent with a progressive failure of local inhibitory restraint. As seizures increased in frequency, there was a gradual increase in the spatial extent of spike-associated glutamate transients associated with interictal spikes. Neurotransmitter imaging thus reveals a progressive collapse of an annulus of feed-forward GABA release, allowing seizures to escape from local inhibitory restraint.

Type: Article
Title: Extracellular glutamate and GABA transients at the transition from interictal spiking to seizures
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/brain/awad336
Publisher version: https://doi.org/10.1093/brain/awad336
Language: English
Additional information: Copyright © The Author(s) 2023. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/bync/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Disinhibition, ictogenesis, paroxysm, neocortex
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-pp.ucl.ac.uk/id/eprint/10178360
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