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

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

Authors :
Shimoda Y
Leite M
Graham RT
Marvin JS
Hasseman J
Kolb I
Looger LL
Magloire V
Kullmann DM
Source :
Brain : a journal of neurology [Brain] 2024 Mar 01; Vol. 147 (3), pp. 1011-1024.
Publication Year :
2024

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.<br /> (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Details

Language :
English
ISSN :
1460-2156
Volume :
147
Issue :
3
Database :
MEDLINE
Journal :
Brain : a journal of neurology
Publication Type :
Academic Journal
Accession number :
37787057
Full Text :
https://doi.org/10.1093/brain/awad336