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.