Cell Reports
Volume 19, Issue 13, 27 June 2017, Pages 2681-2693
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Article
Reliable and Elastic Propagation of Cortical Seizures In Vivo

https://doi.org/10.1016/j.celrep.2017.05.090Get rights and content
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Highlights

  • Seizures spread reliably through cortical microcircuits, within and across layers

  • Seizures recruit supra-granular layers ahead of deep layers

  • Despite relative reliability, recruitment is variable in absolute time (elasticity)

  • Elasticity of ictal progression is shaped by local GABAergic interneurons

Summary

Mapping the fine-scale neural activity that underlies epilepsy is key to identifying potential control targets of this frequently intractable disease. Yet, the detailed in vivo dynamics of seizure progression in cortical microcircuits remain poorly understood. We combine fast (30-Hz) two-photon calcium imaging with local field potential (LFP) recordings to map, cell by cell, the spread of locally induced (4-AP or picrotoxin) seizures in anesthetized and awake mice. Using single-layer and microprism-assisted multilayer imaging in different cortical areas, we uncover reliable recruitment of local neural populations within and across cortical layers, and we find layer-specific temporal delays, suggesting an initial supra-granular invasion followed by deep-layer recruitment during lateral seizure spread. Intriguingly, despite consistent progression pathways, successive seizures show pronounced temporal variability that critically depends on GABAergic inhibition. We propose an epilepsy circuit model resembling an elastic meshwork, wherein ictal progression faithfully follows preexistent pathways but varies flexibly in time, depending on the local inhibitory restraint.

Keywords

two-photon
epilepsy
seizure
4-AP
picrotoxin
calcium
GABA

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