Pathophysiological mechanisms of genetic absence epilepsy in the rat.
Generalized non-convulsive absence seizures are characterized by the occurrence 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 support the use of genetic rodent models, in which spontaneous SWDs occur. 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 recordings from various brain regions and lesion experiments showed that the cortex, the reticular nucleus and the relay nuclei of the thalamus play a predominant role in the development of SWDs. Neither the cortex, nor the thalamus alone can sustain SWDs, indicating that both structures are intimely involved in the genesis of SWDs. Pharmacological data confirmed that both inhibitory and excitatory neurotransmissions are involved in the genesis and control of absence seizures. Whether the generation of SWDs is the result of an excessive cortical excitability, due to an unbalance between inhibition and excitation, or excessive thalamic oscillations, due to abnormal intrinsic neuronal properties under the control of inhibitory GABAergic mechanisms, remains controversial. The thalamo-cortical activity is regulated by several monoaminergic and cholinergic projections. An alteration of the activity of these different ascending inputs may induce a temporary inadequation of the functional state between the cortex and the thalamus and thus promote SWDs. The experimental data are discussed in view of these possible pathophysiological mechanisms.
Danober
L
L
INSERM U 398, Neurobiologie et Neuropharmacologie des épilepsies généralisées, Faculté de Médecine, Strasbourg, France. U398@neurochem.u-strasbg.fr
Deransart
C
C
Depaulis
A
A
Vergnes
M
M
Marescaux
C
C
D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology; D004832:Epilepsy, Absence / Q000235:genetics* / Q000503:physiopathology*; D007245:Inferior Colliculi / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology; D051381:Rats / Q000502:physiology*; D011922:Rats, Mutant Strains / Q000502:physiology; D013378:Substantia Nigra / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D013788:Thalamus / Q000503:physiopathology