Abstracts

Rationale : GABAB receptors located in the reticular and ventrobasal nuclei of the thalamus have been suggested to play a critical role in the genesis of spike-and-wave discharges in rats with spontaneous absence epilepsy (GAERS). In these rats, microinjection of GABAB agonists and antagonists in the ventrobasal nuclei of the thalamus respectively aggravates or suppresses spike-and-wave discharges. Furthermore, these discharges appear to be concomitant with a sustained hyperpolarisation of thalamo-cortical neurons, probably due to activation of GABAB receptors. In order to learn about the involvement of the different subunits of these receptors in the genesis of spike-and-wave discharges, we examined the expression of mRNA coding for GABAB R1a, R1b and R2 heterodimers in the reticular and ventrobasal thalamic nuclei of GAERS and their inbred controls. Methods : In situ hybridization was performed with 35S-labeled riboprobes specific for each subunit and the levels of expression were quantified on individualized neurons after exposure of the brain sections to nuclear emulsion. Results : In the reticular nucleus, the expression of R1a and R2 mRNA was significantly higher in GAERS. In the ventrobasal nuclei (ventrolateral, ventroposterior thalamus), the expression of R2 mRNA was significantly lower in GAERS, whereas R1a and R1b subunits were increased, although in a non significant way. Conclusion : These results suggest that spike-and-wave discharges in GAERS are associated with an increase of expression of R1a/R2 GABAB receptor in the reticular nucleus and a change of this receptor stoechiometry in the ventrobasal nuclei.