Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy
Radiotherapy has shown some efficacy for epilepsies but the insufficient confinement of the radiation dose to the pathological target reduces its indications. Synchrotron-generated X-rays overcome this limitation and allow the delivery of focalized radiation doses to discrete brain volumes via inter...
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doaj-91a668035d714f02bb793ff49306fd852021-03-22T12:39:22ZengElsevierNeurobiology of Disease1095-953X2013-03-0151152160Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsyBenoît Pouyatos0Raphaël Serduc1Mathilde Chipaux2Tanguy Chabrol3Elke Bräuer-Krisch4Christian Nemoz5Hervé Mathieu6Olivier David7Luc Renaud8Yolanda Prezado9Jean Albert Laissue10François Estève11Stéphane Charpier12Antoine Depaulis13Grenoble Institut des Neurosciences, Inserm U836, Université Joseph Fourier, Grenoble, France; Corresponding author at: Grenoble Institut des Neurosciences, Inserm U836, Equipe 11, Bâtiment Edmond J. Safra, Chemin Fortuné Ferrini, 38700 La Tronche. Fax: +33 456520598.Grenoble Institut des Neurosciences, Inserm U836, Université Joseph Fourier, Grenoble, FranceService de Neurochirurgie pédiatrique, Fondation Rothschild, Paris, France; Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC/INSERM, UMR-S 975, CNRS UMR 7225, Paris, FranceGrenoble Institut des Neurosciences, Inserm U836, Université Joseph Fourier, Grenoble, FranceEuropean Synchrotron Research Facility, Biomedical beamline ID17, Grenoble, FranceEuropean Synchrotron Research Facility, Biomedical beamline ID17, Grenoble, FranceGrenoble Institut des Neurosciences, Inserm U836, Université Joseph Fourier, Grenoble, FranceGrenoble Institut des Neurosciences, Inserm U836, Université Joseph Fourier, Grenoble, FranceCentre de Recherche Cerveau et Cognition, CNRS UMR 5549, Toulouse, FranceEuropean Synchrotron Research Facility, Biomedical beamline ID17, Grenoble, FranceInstitute of Pathology, University of Bern, SwitzerlandGrenoble Institut des Neurosciences, Inserm U836, Université Joseph Fourier, Grenoble, FranceCentre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC/INSERM, UMR-S 975, CNRS UMR 7225, Paris, FranceGrenoble Institut des Neurosciences, Inserm U836, Université Joseph Fourier, Grenoble, FranceRadiotherapy has shown some efficacy for epilepsies but the insufficient confinement of the radiation dose to the pathological target reduces its indications. Synchrotron-generated X-rays overcome this limitation and allow the delivery of focalized radiation doses to discrete brain volumes via interlaced arrays of microbeams (IntMRT). Here, we used IntMRT to target brain structures involved in seizure generation in a rat model of absence epilepsy (GAERS). We addressed the issue of whether and how synchrotron radiotherapeutic treatment suppresses epileptic activities in neuronal networks. IntMRT was used to target the somatosensory cortex (S1Cx), a region involved in seizure generation in the GAERS. The antiepileptic mechanisms were investigated by recording multisite local-field potentials and the intracellular activity of irradiated S1Cx pyramidal neurons in vivo. MRI and histopathological images displayed precise and sharp dose deposition and revealed no impairment of surrounding tissues. Local-field potentials from behaving animals demonstrated a quasi-total abolition of epileptiform activities within the target. The irradiated S1Cx was unable to initiate seizures, whereas neighboring non-irradiated cortical and thalamic regions could still produce pathological oscillations. In vivo intracellular recordings showed that irradiated pyramidal neurons were strongly hyperpolarized and displayed a decreased excitability and a reduction of spontaneous synaptic activities. These functional alterations explain the suppression of large-scale synchronization within irradiated cortical networks. Our work provides the first post-irradiation electrophysiological recordings of individual neurons. Altogether, our data are a critical step towards understanding how X-ray radiation impacts neuronal physiology and epileptogenic processes.http://www.sciencedirect.com/science/article/pii/S0969996112003683EpilepsyAnimal modelSpike-wave dischargesRadiotherapySynchrotron X-ray microbeamsIntracellular recordings |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Benoît Pouyatos Raphaël Serduc Mathilde Chipaux Tanguy Chabrol Elke Bräuer-Krisch Christian Nemoz Hervé Mathieu Olivier David Luc Renaud Yolanda Prezado Jean Albert Laissue François Estève Stéphane Charpier Antoine Depaulis |
spellingShingle |
Benoît Pouyatos Raphaël Serduc Mathilde Chipaux Tanguy Chabrol Elke Bräuer-Krisch Christian Nemoz Hervé Mathieu Olivier David Luc Renaud Yolanda Prezado Jean Albert Laissue François Estève Stéphane Charpier Antoine Depaulis Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy Neurobiology of Disease Epilepsy Animal model Spike-wave discharges Radiotherapy Synchrotron X-ray microbeams Intracellular recordings |
author_facet |
Benoît Pouyatos Raphaël Serduc Mathilde Chipaux Tanguy Chabrol Elke Bräuer-Krisch Christian Nemoz Hervé Mathieu Olivier David Luc Renaud Yolanda Prezado Jean Albert Laissue François Estève Stéphane Charpier Antoine Depaulis |
author_sort |
Benoît Pouyatos |
title |
Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy |
title_short |
Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy |
title_full |
Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy |
title_fullStr |
Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy |
title_full_unstemmed |
Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy |
title_sort |
synchrotron x-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2013-03-01 |
description |
Radiotherapy has shown some efficacy for epilepsies but the insufficient confinement of the radiation dose to the pathological target reduces its indications. Synchrotron-generated X-rays overcome this limitation and allow the delivery of focalized radiation doses to discrete brain volumes via interlaced arrays of microbeams (IntMRT). Here, we used IntMRT to target brain structures involved in seizure generation in a rat model of absence epilepsy (GAERS). We addressed the issue of whether and how synchrotron radiotherapeutic treatment suppresses epileptic activities in neuronal networks. IntMRT was used to target the somatosensory cortex (S1Cx), a region involved in seizure generation in the GAERS. The antiepileptic mechanisms were investigated by recording multisite local-field potentials and the intracellular activity of irradiated S1Cx pyramidal neurons in vivo. MRI and histopathological images displayed precise and sharp dose deposition and revealed no impairment of surrounding tissues. Local-field potentials from behaving animals demonstrated a quasi-total abolition of epileptiform activities within the target. The irradiated S1Cx was unable to initiate seizures, whereas neighboring non-irradiated cortical and thalamic regions could still produce pathological oscillations. In vivo intracellular recordings showed that irradiated pyramidal neurons were strongly hyperpolarized and displayed a decreased excitability and a reduction of spontaneous synaptic activities. These functional alterations explain the suppression of large-scale synchronization within irradiated cortical networks. Our work provides the first post-irradiation electrophysiological recordings of individual neurons. Altogether, our data are a critical step towards understanding how X-ray radiation impacts neuronal physiology and epileptogenic processes. |
topic |
Epilepsy Animal model Spike-wave discharges Radiotherapy Synchrotron X-ray microbeams Intracellular recordings |
url |
http://www.sciencedirect.com/science/article/pii/S0969996112003683 |
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