Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.

Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics e...

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Autores principales: Inna Sukhotinsky, Alexander M Chan, Omar J Ahmed, Vikram R Rao, Viviana Gradinaru, Charu Ramakrishnan, Karl Deisseroth, Ania K Majewska, Sydney S Cash
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/1102cb4939e94baebeb2eb38613deae7
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spelling oai:doaj.org-article:1102cb4939e94baebeb2eb38613deae72021-11-18T07:48:00ZOptogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.1932-620310.1371/journal.pone.0062013https://doaj.org/article/1102cb4939e94baebeb2eb38613deae72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23637949/?tool=EBIhttps://doaj.org/toc/1932-6203Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR), a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues.Inna SukhotinskyAlexander M ChanOmar J AhmedVikram R RaoViviana GradinaruCharu RamakrishnanKarl DeisserothAnia K MajewskaSydney S CashPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e62013 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Inna Sukhotinsky
Alexander M Chan
Omar J Ahmed
Vikram R Rao
Viviana Gradinaru
Charu Ramakrishnan
Karl Deisseroth
Ania K Majewska
Sydney S Cash
Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.
description Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR), a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues.
format article
author Inna Sukhotinsky
Alexander M Chan
Omar J Ahmed
Vikram R Rao
Viviana Gradinaru
Charu Ramakrishnan
Karl Deisseroth
Ania K Majewska
Sydney S Cash
author_facet Inna Sukhotinsky
Alexander M Chan
Omar J Ahmed
Vikram R Rao
Viviana Gradinaru
Charu Ramakrishnan
Karl Deisseroth
Ania K Majewska
Sydney S Cash
author_sort Inna Sukhotinsky
title Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.
title_short Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.
title_full Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.
title_fullStr Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.
title_full_unstemmed Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.
title_sort optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/1102cb4939e94baebeb2eb38613deae7
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