The Paroxysmal Depolarizing Shift: The First Cellular Marker of Focal Epileptogenesis

The mechanisms underlying the generation of interictal spikes identified in the electroencephalograms of epileptic patients and animal models of focal epilepsy have become more and more defined as technical advances in the analysis of these events have evolved. Central to this chapter, several investigators have focused on the paroxysmal depolarizing shift (PDS), which is thought to be the intracellular counterpart of the interictal spike generated by neuronal networks and intrinsic membrane conductances in both in vivo and in vitro preparations that mimic focal epileptic disorders. Here, we will review early in vivo experiments, in which the PDS was first identified, as well as later in vitro studies that were performed during GABA receptor antagonism but also during concomitant enhancement of excitatory and inhibitory synaptic mechanisms. Finally, we will review the contribution of intrinsic neuronal mechanisms, and in particular dendritic Ca action potentials, to the generation of the PDS. The findings reviewed here outline some concepts on brain function that have emerged by analyzing the generation of the PDS during the last six decades, and that may play a role in other pathological, and perhaps even physiological, activities.