Elsevier

Neuroscience

Volume 105, Issue 1, 16 July 2001, Pages 181-201
Neuroscience

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

https://doi.org/10.1016/S0306-4522(01)00182-8Get rights and content

Abstract

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.

Section snippets

Experimental procedures

Fifty-seven adult male Wistar rats weighing 280–350 g were used in this study, which included 31 GAERS (from the 39th to 45th generations) and 26 NE rats (from the 31st to 39th generations). The rats were born and raised under standard conditions in our research unit (INSERM U398, Strasbourg, France). All surgical and animal care procedures adhered to the Guidelines for the Use of Animals in Neuroscience Research (1991) and were approved by our national authorities. All efforts were made to

ECoG in undrugged, behaving GAERS and non-epileptic rats

During wakefulness in GAERS rats, most of the spontaneous SWd (SW complexes at about 6–8 Hz) emerged from short episodes (0.5–3 s) of medium-voltage 5–9-Hz oscillations on a background of low-voltage desynchronized ECoG (Fig. 1). Identical short-lasting (1–3 s) bursts of 5–9-Hz oscillations, which were sometimes accompanied by small-amplitude (<0.5 mV) negative spike components, were also recorded during interictal episodes. Such 5–9-Hz oscillation bursts, which were often characterized by

Discussion

Our results demonstrate that, in a genetic model of absence epilepsy, SWd evolve in the TC system from medium-voltage 5–9-Hz (mean=6 Hz) oscillations, which are fairly distinguishable from sleep spindles. Employing dual extracellular recordings, we further show that reticular cells fire in the burst mode almost always before relay neurons during 5–9-Hz oscillations, which often herald the initial stage of the SWd generation. The frequency of occurrence of the SW complexes (mean=6 Hz)

Conclusion

SWd evolve from medium-voltage 5–9-Hz oscillations in the TC system in a genetic model of absence epilepsy. This rhythm is not itself sufficient to initiate SWd, meaning that genetic factors render TC 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 relay neurons during seizures, glutamatergic TC cells might significantly participate in the

Acknowledgements

We are grateful to John W. Crabtree and Martin Deschênes for comments made on a previous version of the manuscript, and Any Boehrer for selecting the epileptic and non-epileptic strains and for her excellent care of the animals. The Institut Fédératif de Recherche en Neuroscience Strasbourgeois is gratefully acknowledged for providing common services. This research was supported by the Clinique Neurologique, the Faculté de Médecine, the Fondation Française pour la Recherche sur l’Epilepsie, the

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