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 t halamocortical 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 neuroleptanalg esia. Short-lasting episodes of medium-voltage 5-9-Hz (mean = 6-Hz) oscilla tions usually emerged spontaneously from a desynchronized electrocorticogra m and in bilateral synchrony in both rat strains. These oscillations were d istinguishable from sleep spindles regarding their internal frequency, dura tion, morphology, and moment of occurrence. Spontaneous spike-and-wave disc harges developed from such synchronized medium-voltage oscillations, the sp ike-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 generatio n of spike-and-wave discharges, dual extracellular recording and juxtacellu lar labelling of relay and reticular neurons were conducted to study the th alamic 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 (inte rburst frequency of up to 6-8 Hz) in relay cells, and of rhythmic bursts (u p to 12-15 Hz) in reticular neurons, these discharging in the burst mode al most always before relay neurons. The discharge frequency of reticular burs ts decelerated to 6 Hz by the beginning of the spike-and-wave discharges. D uring these, relay and reticular neurons usually fired in synchrony a singl e action potential or a high-frequency burst of two or three action potenti als and a high-frequency burst, respectively, about 12 ms before the spike component of the spike-and-wave complexes. The frequency of these correspon ded to the maximal frequency of the thalamocortical burst discharges associ ated with 5-9-Hz oscillations. The patterns of relay and reticular phasic c ellular firings associated with spike-and-wave discharges had temporal char acteristics similar to those associated with medium-voltage 5-9-Hz oscillat ions, 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 lo op give rise to spike-and-wave discharges. Such oscillations are not themse lves sufficient to initiate spike-and-wave discharges, meaning that genetic factors render thalamocortical networks prone to generate epileptic electr ical activity, possibly by decreasing the excitability threshold in reticul ar cells. While these GABAergic neurons play a key role in the synchronizat ion of glutamatergic relay neurons during seizures, relay cells may partici pate significantly in the regulation of the recurrence of the spike-and-wav e complex. Furthermore, it is very likely that synchronization of relay and reticular cellular discharges during absence seizures is generated in part by corticothalamic inputs. (C) 2001 IBRO. Published by Elsevier Science Lt d. All rights reserved.