New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices

Spreading depolarization (SD) is a sudden, large, and synchronous depolarization of principal cells which also involves interneurons and astrocytes. It is followed by depression of neuronal activity, and it slowly propagates across brain regions like cortex or hippocampus. SD is considered to be mec...

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Autores principales:	Yi-Ling Lu, Helen E. Scharfman
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	spreading depression intrinsic optical signal seizures epilepsy experimental model migraine Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/17d3cc908d494a348b6ad8c3460f2d21
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spelling	oai:doaj.org-article:17d3cc908d494a348b6ad8c3460f2d212021-12-01T09:11:19ZNew Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices1662-510210.3389/fncel.2021.761423https://doaj.org/article/17d3cc908d494a348b6ad8c3460f2d212021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncel.2021.761423/fullhttps://doaj.org/toc/1662-5102Spreading depolarization (SD) is a sudden, large, and synchronous depolarization of principal cells which also involves interneurons and astrocytes. It is followed by depression of neuronal activity, and it slowly propagates across brain regions like cortex or hippocampus. SD is considered to be mechanistically relevant to migraine, epilepsy, and traumatic brain injury (TBI), but there are many questions about its basic neurophysiology and spread. Research into SD in hippocampus using slices is often used to gain insight and SD is usually triggered by a focal stimulus with or without an altered extracellular buffer. Here, we optimize an in vitro experimental model allowing us to record SD without focal stimulation, which we call spontaneous. This method uses only an altered extracellular buffer containing 0 mM Mg2+ and 5 mM K+ and makes it possible for simultaneous patch and extracellular recording in a submerged chamber plus intrinsic optical imaging in slices of either sex. We also add methods for quantification and show the quantified optical signal is much more complex than imaging alone would suggest. In brief, acute hippocampal slices were prepared with a chamber holding a submerged slice but with flow of artificial cerebrospinal fluid (aCSF) above and below, which we call interface-like. As soon as slices were placed in the chamber, aCSF with 0 Mg2+/5 K+ was used. Most mouse slices developed SD and did so in the first hour of 0 Mg2+/5 K+ aCSF exposure. In addition, prolonged bursts we call seizure-like events (SLEs) occurred, and the interactions between SD and SLEs suggest potentially important relationships. Differences between rats and mice in different chambers are described. Regarding optical imaging, SD originated in CA3 and the pattern of spread to CA1 and the dentate gyrus was similar in some ways to prior studies but also showed interesting differences. In summary, the methods are easy to use, provide new opportunities to study SD, new insights, and are inexpensive. They support previous suggestions that SD is diverse, and also suggest that participation by the dentate gyrus merits greater attention.Yi-Ling LuHelen E. ScharfmanHelen E. ScharfmanHelen E. ScharfmanHelen E. ScharfmanFrontiers Media S.A.articlespreading depressionintrinsic optical signalseizuresepilepsyexperimental modelmigraineNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Cellular Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	spreading depression intrinsic optical signal seizures epilepsy experimental model migraine Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	spreading depression intrinsic optical signal seizures epilepsy experimental model migraine Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Yi-Ling Lu Helen E. Scharfman Helen E. Scharfman Helen E. Scharfman Helen E. Scharfman New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices
description	Spreading depolarization (SD) is a sudden, large, and synchronous depolarization of principal cells which also involves interneurons and astrocytes. It is followed by depression of neuronal activity, and it slowly propagates across brain regions like cortex or hippocampus. SD is considered to be mechanistically relevant to migraine, epilepsy, and traumatic brain injury (TBI), but there are many questions about its basic neurophysiology and spread. Research into SD in hippocampus using slices is often used to gain insight and SD is usually triggered by a focal stimulus with or without an altered extracellular buffer. Here, we optimize an in vitro experimental model allowing us to record SD without focal stimulation, which we call spontaneous. This method uses only an altered extracellular buffer containing 0 mM Mg2+ and 5 mM K+ and makes it possible for simultaneous patch and extracellular recording in a submerged chamber plus intrinsic optical imaging in slices of either sex. We also add methods for quantification and show the quantified optical signal is much more complex than imaging alone would suggest. In brief, acute hippocampal slices were prepared with a chamber holding a submerged slice but with flow of artificial cerebrospinal fluid (aCSF) above and below, which we call interface-like. As soon as slices were placed in the chamber, aCSF with 0 Mg2+/5 K+ was used. Most mouse slices developed SD and did so in the first hour of 0 Mg2+/5 K+ aCSF exposure. In addition, prolonged bursts we call seizure-like events (SLEs) occurred, and the interactions between SD and SLEs suggest potentially important relationships. Differences between rats and mice in different chambers are described. Regarding optical imaging, SD originated in CA3 and the pattern of spread to CA1 and the dentate gyrus was similar in some ways to prior studies but also showed interesting differences. In summary, the methods are easy to use, provide new opportunities to study SD, new insights, and are inexpensive. They support previous suggestions that SD is diverse, and also suggest that participation by the dentate gyrus merits greater attention.
format	article
author	Yi-Ling Lu Helen E. Scharfman Helen E. Scharfman Helen E. Scharfman Helen E. Scharfman
author_facet	Yi-Ling Lu Helen E. Scharfman Helen E. Scharfman Helen E. Scharfman Helen E. Scharfman
author_sort	Yi-Ling Lu
title	New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices
title_short	New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices
title_full	New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices
title_fullStr	New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices
title_full_unstemmed	New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices
title_sort	new insights and methods for recording and imaging spontaneous spreading depolarizations and seizure-like events in mouse hippocampal slices
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/17d3cc908d494a348b6ad8c3460f2d21
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New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices

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