Laminar Profiles of [K⁺]_O and [Ca²⁺]_O in Region CA1 of the Hippocampus of Kindled Rats

Abstract

Daily repeated tetanic stimulation of mild physiological intensity leads, in many parts of the brain, to the gradual development of an epileptogenic focus. This treatment (kindling) may finally even result in generalized tonic clonic convulsions. Since its first description in 1969 by Goddard [7], this experimental model of epilepsy has drawn considerable attention as one of the few models of permanent plasticity in the adult vertebrate brain. Much work has been devoted to defining optimal parameters for stimulation, to determine the sensitivity for kindling of different regions of the brain in a variety of species, and to exclude the phenomenon from being an implantation artifact (reviews are given by Racine [29] and McNamara et al. [20]. Despite the fact that a lot of knowledge has been acquired in this way, still little is known about the cellular mechanisms that underlie kindling epilepsy. Changes in polarity of epileptiform transients recorded in vivo during kindling epileptogenesis suggested that some dendritic process might be involved [16, 32]. Furthermore, it is known from several other models of epilepsy that variations in the concentrations of calcium and potassium in the extracellular space play an important role in the stability of neuronal circuits and that the concentrations of these ions can vary considerably during epileptiform activity [10,13, 23, 24–26, 31, 33]. In order to investigate the underlying mechanisms of kindling in more detail at a cellular level, we combined the in vivo model of kindling with the in vitro method of hippocampal slices [3,11,18]. The in vitro technique enabled us to record accurately, in tissue obtained from kindled rats, the laminar profiles of changes in extracellular potassium [K⁺]_O and extracellular calcium [Ca²⁺]_O induced by different methods.