Alterations in GABA(A) receptor alpha 1 and alpha 4 subunit mRNA levels inthalamic relay nuclei following absence-like seizures in rats

Modification of GABA(A) receptor mRNA levels by seizure activity can regula te general neuronal excitability. The possibility of absence seizure-induce d alteration in GABA(A) receptor alpha 1, alpha 4, beta 2, and gamma 2 subu nit gene expression in thalamic relay nuclei was studied in a rat model of absence seizures induced by gamma-hydroxybutyric acid (GHB). We observed a marked increase in alpha 1 mRNA and a corresponding decrease in alpha 4 mRN A in thalamic relay nuclei 2-4 h after the onset of GHB-induced absence sei zures (when the seizures were terminating). These changes were selective to these alpha isoforms as neither beta 2 nor gamma 2 mRNA changed following seizures and occurred only in thalamic relay nuclei but not in hippocampus, a structure from which absence seizures do not evolve. The alterations in alpha 1 and alpha 4 mRNA persisted until about 12 h, and by 24 h after the seizure-onset the mRNA levels normalized Blocking GHB-seizures produced no change in the levels of alpha 1 and alpha 4 mRNA in thalamic relay nuclei, suggesting that seizures themselves were responsible for mRNA alterations, In order to determine if absence seizure-induced changes in alpha 1 and alp ha 4 mRNA had any physiological significance, GHB was readministered in rat s 6 and 24 h after the onset of seizures. The total duration of GHB-seizure s was found to be significantly decreased when GHB was readministered at 6 h but not 24 h after the seizure-onset. These results suggest that absence seizures regulate GABA(A) receptor alpha 1 and alpha 4 gene expression in t halamic relay nuclei as a compensatory mechanism by which absence seizures are terminated. (C) 1998 Academic Press.