Combined experimental/simulation studies of cellular and network mechanisms of epileptogenesis in vitro and in vivo.

The electrical correlates of clinical seizures, and of experimental models of seizures, are recognized because neurons behave differently than normal. Individual neurons do unusual things, and neuronal activities become correlated with each other in ways that are not observed under physiologic conditions. Single neurons may fire bursts of action potentials superimposed on large depolarizations, and the bursts may recur rhythmically over a wide range of frequencies (<1 Hz to 25 Hz); periods of noisy subthreshold activity can occur; and firing can even be suppressed in some neurons. At the population level, nearby neurons tend to fire action potentials, or generate bursts, that are temporally locked together on a few-milliseconds time scale, so that large voltage transients are generated in extracellular fields. Very fast oscillations (>80 Hz) in neuronal aggregates may occur before, during, or after such large field potentials. Finally, cellular activities may even be correlated across large brain regions. The authors review some of the means by which cellular intrinsic properties, synaptic interactions, and electrical coupling via gap junctions, all contribute to the anomalous population activities characteristic of seizures. Also reviewed are some of the data suggesting that the requisite gap junctions are located on the axons of glutamatergic neurons.