Medium-voltage 5-9-Hz oscillations give rise to spike-and-wave discharges in a genetic model of absence epilepsy: in vivo dual extracellular recording of thalamic relay and reticular neurons.
In humans with absence epilepsy, spike-and-wave discharges develop in the thalamocortical system during quiet immobile wakefulness or drowsiness. The present study examined the initial stage of the spontaneous development of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg. Bilateral electrocorticograms were recorded in epileptic and non-epileptic rats under freely moving and undrugged conditions and under neuroleptanalgesia. Short-lasting episodes of medium-voltage 5-9-Hz (mean=6-Hz) oscillations usually emerged spontaneously from a desynchronized electrocorticogram and in bilateral synchrony in both rat strains. These oscillations were distinguishable from sleep spindles regarding their internal frequency, duration, morphology, and moment of occurrence. Spontaneous spike-and-wave discharges developed from such synchronized medium-voltage oscillations, the spike-and-wave complex occurring at the same frequency as the 5-9-Hz wave. Because the thalamus is thought to play a significant role in the generation of spike-and-wave discharges, dual extracellular recording and juxtacellular labelling of relay and reticular neurons were conducted to study the thalamic cellular mechanisms associated with the generation of spike-and-wave discharges. During medium-voltage 5-9-Hz oscillations, discharges of relay and reticular cells had identical patterns in epileptic and non-epileptic rats, consisting of occasional single action potentials and/or bursts (interburst frequency of up to 6-8 Hz) in relay cells, and of rhythmic bursts (up to 12-15 Hz) in reticular neurons, these discharging in the burst mode almost always before relay neurons. The discharge frequency of reticular bursts decelerated to 6 Hz by the beginning of the spike-and-wave discharges. During these, relay and reticular neurons usually fired in synchrony a single action potential or a high-frequency burst of two or three action potentials and a high-frequency burst, respectively, about 12 ms before the spike component of the spike-and-wave complexes. The frequency of these corresponded to the maximal frequency of the thalamocortical burst discharges associated with 5-9-Hz oscillations. The patterns of relay and reticular phasic cellular firings associated with spike-and-wave discharges had temporal characteristics similar to those associated with medium-voltage 5-9-Hz oscillations, suggesting that these normal and epileptic oscillations are underlain by similar thalamic cellular mechanisms. In conclusion, medium-voltage 5-9-Hz oscillations in the thalamocortical loop give rise to spike-and-wave discharges. Such oscillations are not themselves sufficient to initiate spike-and-wave discharges, meaning that genetic factors render thalamocortical networks prone to generate epileptic electrical activity, possibly by decreasing the excitability threshold in reticular cells. While these GABAergic neurons play a key role in the synchronization of glutamatergic relay neurons during seizures, relay cells may participate significantly in the regulation of the recurrence of the spike-and-wave complex. Furthermore, it is very likely that synchronization of relay and reticular cellular discharges during absence seizures is generated in part by corticothalamic inputs.
Pinault
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INSERM U398, Neurobiologie et Neuropharmacologie des Epilepsies Généralisées, Faculté de Médecine, 11 rue Humann, F-67085, Strasbourg, France. pinault@neurochem.u-strasbg.fr
Vergnes
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Marescaux
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000473:pathology / Q000503:physiopathology*; D005283:Fentanyl / Q000494:pharmacology; D007150:Immunohistochemistry; D008239:Lysine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D013788:Thalamus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D000701:Analgesics, Opioid; C013411:biocytin; D008239:Lysine; D005283:Fentanyl