A possible role for gap junctions in generation of very fast EEG oscillations preceding the onset of, and perhaps initiating, seizures

Purpose: We propose an experimentally and clinically testable hypothesis. c oncerning the origin of very fast (>-70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures. Methods. Subdural EEG recordings were obtained from children with focal cor tical dysplasias and intractable seizures. Intra- and extracellular recordi ngs were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath-applied tetramethylamine (an intracellular a lkalinizing agent, that opens gap junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solu tion. Detailed network simulations were performed, the better to understand the cellular mechanisms underlying oscillations. A major feature of the si mulations was inclusion of axon-axon gap junctions between principal neuron s, as supported by recent experimental data. Results: Very fast oscillations were found in children before seizure onset , but also superimposed on bursts during the seizure, and on interictal bur sts. In slice experiments, very fast oscillations had previously been seen on interictal-like bursts, we now show such oscillations before. between, a nd after epileptiform bursts. Very fast oscillations were also seen superim posed on gamma (30-70 Hz) oscillations induced by carbachol or hypertonic K i, and in the latter case, very fast oscillations became continuous when ch emical synapses were blocked. Simulations replicate these data, when axonal gap junctions are included. Conclusions: Electrical coupling between principal neurons, perhaps via axo nal gap junctions, could underlie very fast population oscillations, in sei zure-prone brain, but possibly also in normal brain. The anticonvulsant pot ential of gap-junction blockers such as carbenoxolone, now in clinical use for treatment of ulcer disease, should be considered.