Abstract
SummarySTXBP1 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.
Highlights
Network analysis of spatiotemporal patterns of brain activity is crucial to our understanding of normal, and pathological, brain states
Data from functional magnetic resonance imaging, in vitro calcium imaging, local field potential (LFP), and/or multi-electrode array recordings have converged on an observation that neural networks operate at a dynamic balance between phases of order and disorder
Studying these network phenomena in vivo under disease conditions is relatively rare, using magnetoencephalography techniques, Arviv et al demonstrated that the brains of patients with adult refractory epilepsy were characterized by larger neuronal avalanches during interictal periods (Arviv et al, 2016)
Summary
Network analysis of spatiotemporal patterns of brain activity is crucial to our understanding of normal, and pathological, brain states. Brief neuronal cascades are not limited to more complex nervous systems and were recently observed by Ponce-Alvarez and colleagues using a brain-wide calcium imaging approach in wild-type larval transgenic zebrafish expressing genetically encoded calcium indicators (GCaMPs) (Ponce-Alvarez et al, 2018). Studying these network phenomena in vivo under disease conditions is relatively rare, using magnetoencephalography techniques, Arviv et al demonstrated that the brains of patients with adult refractory epilepsy were characterized by larger neuronal avalanches during interictal periods (Arviv et al, 2016). Whether similar patterns of network activity are present in a genetic form of epilepsy in vivo and at early stages of neurodevelopment is currently unknown
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