Gap Junctions and the Very Fast Oscillations (>70 Hz) That Precede Seizures

Electrographic seizure discharges are frequently preceded by runs (hundreds of 
ms to a few seconds) of very fast oscillations. This phenomenon has been observed
in human patients with subdural grid and depth electrode recordings; in anesthetized 
cats in vivo, by the late Mircea Steriade and colleagues; and in in vitro models, 
using hippocampal and neocortical slices.  Experimental and network modeling work 
indicate that very fast oscillations are generated by electrically coupled ensembles 
of principal neurons, with the site of electrical coupling in the axons. This conclusion 
is supported by simultaneous recordings of soma and axon in vitro, by the pharmacological 
block of very fast oscillations with halothane and other gap junction-blocking compounds 
(in vitro and in vivo), and by dye coupling captured with confocal imaging between 
axons.  More recently, gap junctions have been imaged ultrastructurally, between 
mossy fiber axons, including freeze-fracture immunolabeling that demonstrates connexin36. 
It remains to be determined if the very fast oscillations themselves causally initiate 
seizures, or rather are a flag for the presence of altered cortical structure and 
cellular environment which independently initiate seizures.