In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish

Summary: STXBP1 mutations are associated with encephalopathy, developmental delay, intellectual disability, and epilepsy. While neural networks are known to operate at a critical state in the healthy brain, network behavior during pathological epileptic states remains unclear. Examining activity dur...

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Main Authors: Jing Liu, Kathryn A. Salvati, Scott C. Baraban
Format: Article
Language:English
Published: Elsevier 2021-06-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004221005265
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author Jing Liu
Kathryn A. Salvati
Scott C. Baraban
author_facet Jing Liu
Kathryn A. Salvati
Scott C. Baraban
author_sort Jing Liu
collection DOAJ
description Summary: STXBP1 mutations are associated with encephalopathy, developmental delay, intellectual disability, and epilepsy. While neural networks are known to operate at a critical state in the healthy brain, network behavior during pathological epileptic states remains unclear. Examining activity during periods between well-characterized ictal-like events (i.e., interictal period) could provide a valuable step toward understanding epileptic networks. To study these networks in the context of STXBP1 mutations, we combine a larval zebrafish model with in vivo fast confocal calcium imaging and extracellular local field potential recordings. Stxbp1b mutants display transient periods of elevated activity among local clusters of interacting neurons. These network “cascade” events were significantly larger in size and duration in mutants. At mesoscale resolution, cascades exhibit neurodevelopmental abnormalities. At single-cell scale, we describe spontaneous hyper-synchronized neuronal ensembles. That calcium imaging reveals uniquely disordered brain states during periods between pathological ictal-like seizure events is striking and represents a potential interictal biomarker.
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spelling doaj.art-1b3fd895552e4e51ab633cc03b8ad3212022-12-21T18:51:08ZengElsevieriScience2589-00422021-06-01246102558In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafishJing Liu0Kathryn A. Salvati1Scott C. Baraban2Epilepsy Research Laboratory and Weill Institute for Neuroscience, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94122, USAEpilepsy Research Laboratory and Weill Institute for Neuroscience, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94122, USAEpilepsy Research Laboratory and Weill Institute for Neuroscience, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94122, USA; Corresponding authorSummary: STXBP1 mutations are associated with encephalopathy, developmental delay, intellectual disability, and epilepsy. While neural networks are known to operate at a critical state in the healthy brain, network behavior during pathological epileptic states remains unclear. Examining activity during periods between well-characterized ictal-like events (i.e., interictal period) could provide a valuable step toward understanding epileptic networks. To study these networks in the context of STXBP1 mutations, we combine a larval zebrafish model with in vivo fast confocal calcium imaging and extracellular local field potential recordings. Stxbp1b mutants display transient periods of elevated activity among local clusters of interacting neurons. These network “cascade” events were significantly larger in size and duration in mutants. At mesoscale resolution, cascades exhibit neurodevelopmental abnormalities. At single-cell scale, we describe spontaneous hyper-synchronized neuronal ensembles. That calcium imaging reveals uniquely disordered brain states during periods between pathological ictal-like seizure events is striking and represents a potential interictal biomarker.http://www.sciencedirect.com/science/article/pii/S2589004221005265Optical imagingMolecular neuroscienceCellular neuroscience
spellingShingle Jing Liu
Kathryn A. Salvati
Scott C. Baraban
In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish
iScience
Optical imaging
Molecular neuroscience
Cellular neuroscience
title In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish
title_full In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish
title_fullStr In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish
title_full_unstemmed In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish
title_short In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish
title_sort in vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish
topic Optical imaging
Molecular neuroscience
Cellular neuroscience
url http://www.sciencedirect.com/science/article/pii/S2589004221005265
work_keys_str_mv AT jingliu invivocalciumimagingrevealsdisorderedinterictalnetworkdynamicsinepilepticstxbp1bzebrafish
AT kathrynasalvati invivocalciumimagingrevealsdisorderedinterictalnetworkdynamicsinepilepticstxbp1bzebrafish
AT scottcbaraban invivocalciumimagingrevealsdisorderedinterictalnetworkdynamicsinepilepticstxbp1bzebrafish