Closely spaced recurrent hippocampal seizures elicit two types of heightened epileptogenesis: a rapidly developing, transient kindling and a slowly developing, enduring kindling

Abstract

Kindling is widely accepted as a model of chronic epilepsy as well as a model of plasticity in the nervous system. Conventional kindling studies have used infrequent stimuli (separated by many hours) to establish a fully kindled state in which enhanced responses (kindled motor seizures and protracted afterdischarges) are consistently triggered by stimuli that initially did not elicit such responses. The enhanced responses occur even after a prolonged stimulus-free interval. Whereas the establishment of a kindled state with traditional stimulus protocols takes several weeks, our previous work showed that kindling could take place much more quickly when the interstimulus interval was set at 30 min (rapid kindling). In this report we tested whether rapid kindling protocols share with traditional kindling protocols the ability to establish a fully kindled state. Using different stimulus protocols involving recurrent hippocampal seizures, we characterized two types of kindling. ‘Rapid kindling’ developed over hours, but was transient, with a decay rate of a few days so that a fully kindled state did not persist. In contrast, ‘slow kindling’ developed over several weeks and was enduring, apparently permanent, being associated with a fully kindled state. These findings suggest that, while having certain similarities, the two types of kindling arise from dissimilar mechanisms. The existence of these two types of kindling has implications for epileptogenesis in humans. Moreover, the protocols developed in this work provide a useful means to control for the effects of seizures that are not related to mechanisms underlying a fully kindled state.