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The Effects of Optogenetic Activation of Astrocytes on Spike-and-Wave Discharges in Genetic Absence Epileptic Rats

Ozgur, Merve; Özyurt, Mustafa Görkem; Arkan, Sertan; Cavdar, Safiye; (2022) The Effects of Optogenetic Activation of Astrocytes on Spike-and-Wave Discharges in Genetic Absence Epileptic Rats. Annals of Neurosciences 10.1177/09727531211072423. (In press). Green open access

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Abstract

Background: Absence seizures (petit mal seizures) are characterized by a brief loss of consciousness without loss of postural tone. The disease is diagnosed by an electroencephalogram (EEG) showing spike–wave discharges (SWD) caused by hypersynchronous thalamocortical (TC) oscillations. There has been an explosion of research highlighting the role of astrocytes in supporting and modulating neuronal activity. Despite established in vitro evidence, astrocytes’ influence on the TC network remains to be elucidated in vivo in the absence epilepsy (AE). Purpose: In this study, we investigated the role of astrocytes in the generation and modulation of SWDs. We hypothesize that disturbances in astrocytes’ function may affect the pathomechanism of AE. Methods: To direct the expression of channelrhodopsin-2 (ChR2) rAAV8-GFAP-ChR2(H134R)-EYFP or to control the effect of surgical intervention, AAV-CaMKIIa-EYFP was injected into the ventrobasal nucleus (VB) of the thalamus of 18 animals. After four weeks following the injection, rats were stimulated using blue light (~473 nm) and, simultaneously, the electrophysiological activity of the frontal cortical neurons was recorded for three consecutive days. The animals were then perfused, and the brain tissue was analyzed by confocal microscopy. Results: A significant increase in the duration of SWD without affecting the number of SWD in genetic absence epileptic rats from Strasbourg (GAERS) compared to control injections was observed. The duration of the SWD was increased from 12.50 ± 4.41 s to 17.44 ± 6.07 following optogenetic stimulation in GAERS. The excitation of the astrocytes in Wistar Albino Glaxo Rijswijk (WAG-Rij) did not change the duration of SWD; however, stimulation resulted in a significant increase in the number of SWD from 18.52 ± 11.46 bursts/30 min to 30.17 ± 18.43 bursts/30 min. Whereas in control injection, the duration and the number of SWDs were similar at pre- and poststimulus. Both the background and poststimulus average firing rates of the SWD in WAG-Rij were significantly higher than the firing recorded in GAERS. Conclusion: These findings suggest that VB astrocytes play a role in modulating the SWD generation in both rat models with distinct mechanisms and can present an essential target for the possible therapeutic approach for AE.

Type: Article
Title: The Effects of Optogenetic Activation of Astrocytes on Spike-and-Wave Discharges in Genetic Absence Epileptic Rats
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/09727531211072423
Publisher version: https://doi.org/10.1177/09727531211072423
Language: English
Additional information: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/).
Keywords: Optogenetics, Spike-and-wave discharges, Typical absence epilepsy, GAERS, WAG-Rij
UCL classification: 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 > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/10145543
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