PATHOPHYSIOLOGICAL MECHANISMS OF GENETIC ABSENCE EPILEPSY IN THE RAT

Generalized non-convulsive absence seizures are characterized by the o ccurrence of synchronous and bilateral spike and wave discharges (SWDs ) on the electroencephalogram, that are concomitant with a behavioral arrest. Many similarities between rodent and human absence seizures su pport the use of genetic rodent models, in which spontaneous SWDs occu r. This review summarizes data obtained on the neurophysiological and neurochemical mechanisms of absence seizures with special emphasis on the Genetic Absence Epilepsy Rats from Strasbourg (GAERS). EEG recordi ngs from various brain regions and lesion experiments showed that the cortex, the reticular nucleus and the relay nuclei of the thalamus pla y a predominant role in the development of SWDs. Neither the cortex, n or the thalamus alone can sustain SWDs, indicating that both structure s are intimely involved in the genesis of SWDs. Pharmacological data c onfirmed that both inhibitory and excitatory neurotransmissions are in volved in the genesis and control of absence seizures. Whether the gen eration of SWDs is the result of an excessive cortical excitability, d ue to an unbalance between inhibition and excitation, or excessive tha lamic oscillations, due to abnormal intrinsic neuronal properties unde r the control of inhibitory GABAergic mechanisms, remains controversia l. The thalamo-cortical activity is regulated by several monoaminergic and cholinergic projections. An alteration of the activity of these d ifferent ascending inputs may induce a temporary inadequation of the f unctional state between the cortex and the thalamus and thus promote S WDs. The experimental data are discussed in view of these possible pat hophysiological mechanisms. (C) 1998 Elsevier Science Ltd. All rights reserved.