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In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light-activated chloride channel, stGtACR2.
Acharya, Anirudh R; Larsen, Lars Emil; Delbeke, Jean; Wadman, Wytse J; Vonck, Kristl; Meurs, Alfred; Boon, Paul; Raedt, Robrecht.
Afiliación
  • Acharya AR; 4BRAIN Team, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Larsen LE; 4BRAIN Team, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Delbeke J; 4BRAIN Team, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Wadman WJ; 4BRAIN Team, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Vonck K; 4BRAIN Team, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Meurs A; 4BRAIN Team, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Boon P; 4BRAIN Team, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Raedt R; 4BRAIN Team, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
CNS Neurosci Ther ; 29(3): 907-916, 2023 03.
Article en En | MEDLINE | ID: mdl-36482869
AIMS: The blue light-sensitive chloride-conducting opsin, stGtACR2, provides potent optogenetic silencing of neurons. The present study investigated whether activation of stGtACR2 in granule cells of the dentate gyrus (DG) inhibits epileptic afterdischarges in a rat model. METHODS: Rats were bilaterally injected with 0.9 µl of AAV2/7-CaMKIIα-stGtACR2-fusionred in the DG. Three weeks later, afterdischarges were recorded from the DG by placing an optrode at the injection site and a stimulation electrode in the perforant path (PP). Afterdischarges were evoked every 10 min by unilateral electrical stimulation of the PP (20 Hz, 10 s). During every other afterdischarge, the DG was illuminated for 5 or 30 s, first ipsilaterally and then bilaterally to the PP stimulation. The line length metric of the afterdischarges was compared between illumination conditions. RESULTS: Ipsilateral stGtACR2 activation during afterdischarges decreased the local field potential line length only during illumination and specifically at the illuminated site but did not reduce afterdischarge duration. Bilateral illumination did not terminate the afterdischarges. CONCLUSION: Optogenetic inhibition of excitatory neurons using the blue-light sensitive chloride channel stGtACR2 reduced the amplitude of electrically induced afterdischarges in the DG at the site of illumination, but this local inhibitory effect was insufficient to reduce the duration of the afterdischarge.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Cloruro / Epilepsia Límite: Animals Idioma: En Revista: CNS Neurosci Ther Asunto de la revista: NEUROLOGIA / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Cloruro / Epilepsia Límite: Animals Idioma: En Revista: CNS Neurosci Ther Asunto de la revista: NEUROLOGIA / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido