title: Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy.
abstract: 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.
authors.affiliation: Grenoble Institut des Neurosciences, Inserm U836, Université Joseph Fourier, Grenoble, France. bpouyatos@gmail.com
authors.forename: Benoît
authors.initials: B
authors.lastname: Pouyatos
authors.forename: Raphaël
authors.initials: R
authors.lastname: Serduc
authors.forename: Mathilde
authors.initials: M
authors.lastname: Chipaux
authors.forename: Tanguy
authors.initials: T
authors.lastname: Chabrol
authors.forename: Elke
authors.initials: E
authors.lastname: Bräuer-Krisch
authors.forename: Christian
authors.initials: C
authors.lastname: Nemoz
authors.forename: Hervé
authors.initials: H
authors.lastname: Mathieu
authors.forename: Olivier
authors.initials: O
authors.lastname: David
authors.forename: Luc
authors.initials: L
authors.lastname: Renaud
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Prezado
authors.forename: Jean Albert
authors.initials: JA
authors.lastname: Laissue
authors.forename: François
authors.initials: F
authors.lastname: Estève
authors.forename: Stéphane
authors.initials: S
authors.lastname: Charpier
authors.forename: Antoine
authors.initials: A
authors.lastname: Depaulis
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000503:physiopathology / Q000532:radiotherapy*; D005260:Female; D009415:Nerve Net / Q000503:physiopathology / Q000528:radiation effects*; D051381:Rats; D013003:Somatosensory Cortex / Q000503:physiopathology / Q000528:radiation effects*; D014964:X-Ray Therapy / Q000379:methods