Kindling Induces Long-Term Changes in Gene Expression

Abstract

Kindling is a model of epileptogenesis which involves permanent neuronal changes resulting in a hyperexcitable state in a population of neurons51,57,96 The kindled state is achieved by repeated subconvulsive stimulations in a defined pattern which eventually elicit a seizure25. The development of the kindled state is progressive. Early in the protocol the stimulations produce focal afterdischarges and later in the paradigm generalized electrographic and behavioral seizures are produced. Once a predefined number of class 5 behavioral seizures74 is elicited the animal is considered kindled. If a sufficient number of seizures are produced, the animal will exhibit spontaneous seizures68. The kindled state is permanent for the life of the animal in that subconvulsive stimulations can produce a seizure months after the last stimulation induced seizure. A variety of kindling protocols exist. The stimulations can be either electrical25 or chemical97. Traditionally electrical stimulations were administered once a day for several weeks; however, Lothman et al.50 determined that the kindled state could be attained in one day with electrical stimulations administered every 5 min. The stimulations can be applied to different brain regions such as the hippocampus, amygdala, perforant path, septum, entorhinal cortex, piriform cortex or perirhinal cortex to attain the kindled state17,51,52,96.