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In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light‐activated chloride channel, stGtACR2

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 bilater...

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Autores principales: Acharya, Anirudh R., Larsen, Lars Emil, Delbeke, Jean, Wadman, Wytse J., Vonck, Kristl, Meurs, Alfred, Boon, Paul, Raedt, Robrecht
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928558/
https://www.ncbi.nlm.nih.gov/pubmed/36482869
http://dx.doi.org/10.1111/cns.14029
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author Acharya, Anirudh R.
Larsen, Lars Emil
Delbeke, Jean
Wadman, Wytse J.
Vonck, Kristl
Meurs, Alfred
Boon, Paul
Raedt, Robrecht
author_facet Acharya, Anirudh R.
Larsen, Lars Emil
Delbeke, Jean
Wadman, Wytse J.
Vonck, Kristl
Meurs, Alfred
Boon, Paul
Raedt, Robrecht
author_sort Acharya, Anirudh R.
collection PubMed
description 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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spelling pubmed-99285582023-02-16 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 CNS Neurosci Ther Original Articles 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. John Wiley and Sons Inc. 2022-12-08 /pmc/articles/PMC9928558/ /pubmed/36482869 http://dx.doi.org/10.1111/cns.14029 Text en © 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Acharya, Anirudh R.
Larsen, Lars Emil
Delbeke, Jean
Wadman, Wytse J.
Vonck, Kristl
Meurs, Alfred
Boon, Paul
Raedt, Robrecht
In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light‐activated chloride channel, stGtACR2
title In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light‐activated chloride channel, stGtACR2
title_full In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light‐activated chloride channel, stGtACR2
title_fullStr In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light‐activated chloride channel, stGtACR2
title_full_unstemmed In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light‐activated chloride channel, stGtACR2
title_short In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light‐activated chloride channel, stGtACR2
title_sort in vivo inhibition of epileptiform afterdischarges in rat hippocampus by light‐activated chloride channel, stgtacr2
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928558/
https://www.ncbi.nlm.nih.gov/pubmed/36482869
http://dx.doi.org/10.1111/cns.14029
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