Preferential superficial cortical layer activation during seizure propagation.

OBJECTIVE: Focal cortical seizures travel long distances from the onset zone, but the long-distance propagation pathways are uncertain. In vitro and in vivo imaging techniques have investigated the local spread of seizures but did not elucidate long-distance spread. Furthermore, classical studies in slices suggested seizure spread locally along deep cortical layers, whereas more recent in vivo imaging studies posit a role for superficial cortical layers in local spread. METHODS: We imaged seizure-activated neurons using activity reporter mice and measured local field potentials (LFPs) using microelectrode arrays to map cortical seizure propagation in awake mice. RESULTS: Frontal lobe onset seizures activate more neurons in superficial layers 2-3 than deep layers 5-6 throughout the cortex. LFP recordings demonstrate that seizures spread faster through the superficial than deep layers over long cortical distances of 3.5 mm. We also show that monosynaptically connected long-distance neurons are in the seizure circuit. SIGNIFICANCE: We propose that long-distance cortical seizure spread occurs preferentially via synaptically connected superficial cortical neurons.