期刊
JOURNAL OF NEUROSCIENCE
卷 39, 期 43, 页码 8562-8575出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3176-18.2019
关键词
calcium imaging; epilepsy; interneurons; microseizures; seizures; two-photon
资金
- Deutsche Forschungsgemeinschaft (DFG) [WE 5517/1-1]
- NEI [DP1EY024503, R01EY011787]
- NIMH [R01MH101218, R01MH100561, R01MH115900]
- DARPA SIMPLEX [N66001-15-C-4032]
- U.S. Army Research Laboratory
- U.S. Army Research Office [W911NF-12-1-0594]
Understanding seizure formation and spread remains a critical goal of epilepsy research. We used fast in vivo two-photon calcium imaging in male mouse neocortex to reconstruct, with single-cell resolution, the dynamics of acute (4-aminopyridine) focal cortical seizures as they originate within a spatially confined seizure initiation site (intrafocal region), and subsequently propagate into neighboring cortical areas (extrafocal region). We find that seizures originate as local neuronal ensembles within the initiation site. This abnormal hyperactivity engages increasingly larger areas in a saltatory fashion until it breaks into neighboring cortex, where it proceeds smoothly and is then detected electrophysiologically (LFP). Interestingly, PV inhibitory interneurons have spatially heterogeneous activity in intrafocal and extrafocal territories, ruling out a simple role of inhibition in seizure formation and spread. We propose a two-step model for the progression of focal seizures, where neuronal ensembles activate first, generating a microseizure, followed by widespread neural activation in a traveling wave through neighboring cortex during macroseizures.
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