Control of in vivo ictogenesis via endogenous synaptic pathways

Abstract The random nature of seizures poses difficult challenges for epilepsy research. There is great need for a reliable method to control the pathway to seizure onset, which would allow investigation of the mechanisms of ictogenesis and optimization of treatments. Our hypothesis is that increase...

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Autores principales:	Hiram Luna-Munguia, Phillip Starski, Wu Chen, Stephen Gliske, William C. Stacey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a7344e6850334a85a66134665b8d8115
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spelling	oai:doaj.org-article:a7344e6850334a85a66134665b8d81152021-12-02T16:06:36ZControl of in vivo ictogenesis via endogenous synaptic pathways10.1038/s41598-017-01450-82045-2322https://doaj.org/article/a7344e6850334a85a66134665b8d81152017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01450-8https://doaj.org/toc/2045-2322Abstract The random nature of seizures poses difficult challenges for epilepsy research. There is great need for a reliable method to control the pathway to seizure onset, which would allow investigation of the mechanisms of ictogenesis and optimization of treatments. Our hypothesis is that increased random afferent synaptic activity (i.e. synaptic noise) within the epileptic focus is one endogenous method of ictogenesis. Building upon previous theoretical and in vitro work showing that synaptic noise can induce seizures, we developed a novel in vivo model of ictogenesis. By increasing the excitability of afferent connections to the hippocampus, we control the risk of temporal lobe seizures during a specific time period. The afferent synaptic activity in the hippocampus was modulated by focal microinjections of potassium chloride into the nucleus reuniens, during which the risk of seizure occurrence increased substantially. The induced seizures were qualitatively and quantitatively indistinguishable from spontaneous ones. This model thus allows direct control of the temporal lobe seizure threshold via endogenous pathways, providing a novel tool in which to investigate the mechanisms and biomarkers of ictogenesis, test for seizure threshold, and rapidly tune antiseizure treatments.Hiram Luna-MunguiaPhillip StarskiWu ChenStephen GliskeWilliam C. StaceyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiram Luna-Munguia Phillip Starski Wu Chen Stephen Gliske William C. Stacey Control of in vivo ictogenesis via endogenous synaptic pathways
description	Abstract The random nature of seizures poses difficult challenges for epilepsy research. There is great need for a reliable method to control the pathway to seizure onset, which would allow investigation of the mechanisms of ictogenesis and optimization of treatments. Our hypothesis is that increased random afferent synaptic activity (i.e. synaptic noise) within the epileptic focus is one endogenous method of ictogenesis. Building upon previous theoretical and in vitro work showing that synaptic noise can induce seizures, we developed a novel in vivo model of ictogenesis. By increasing the excitability of afferent connections to the hippocampus, we control the risk of temporal lobe seizures during a specific time period. The afferent synaptic activity in the hippocampus was modulated by focal microinjections of potassium chloride into the nucleus reuniens, during which the risk of seizure occurrence increased substantially. The induced seizures were qualitatively and quantitatively indistinguishable from spontaneous ones. This model thus allows direct control of the temporal lobe seizure threshold via endogenous pathways, providing a novel tool in which to investigate the mechanisms and biomarkers of ictogenesis, test for seizure threshold, and rapidly tune antiseizure treatments.
format	article
author	Hiram Luna-Munguia Phillip Starski Wu Chen Stephen Gliske William C. Stacey
author_facet	Hiram Luna-Munguia Phillip Starski Wu Chen Stephen Gliske William C. Stacey
author_sort	Hiram Luna-Munguia
title	Control of in vivo ictogenesis via endogenous synaptic pathways
title_short	Control of in vivo ictogenesis via endogenous synaptic pathways
title_full	Control of in vivo ictogenesis via endogenous synaptic pathways
title_fullStr	Control of in vivo ictogenesis via endogenous synaptic pathways
title_full_unstemmed	Control of in vivo ictogenesis via endogenous synaptic pathways
title_sort	control of in vivo ictogenesis via endogenous synaptic pathways
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a7344e6850334a85a66134665b8d8115
work_keys_str_mv	AT hiramlunamunguia controlofinvivoictogenesisviaendogenoussynapticpathways AT phillipstarski controlofinvivoictogenesisviaendogenoussynapticpathways AT wuchen controlofinvivoictogenesisviaendogenoussynapticpathways AT stephengliske controlofinvivoictogenesisviaendogenoussynapticpathways AT williamcstacey controlofinvivoictogenesisviaendogenoussynapticpathways
_version_	1718384980721139712

Control of in vivo ictogenesis via endogenous synaptic pathways

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