Third, mutations in the b3-v2 subun

Third, mutations in the b3-v2 subunit of the GABAA receptor in CAE show reduced a1b3-v2(P11S)g2S, a1b3-v2(S15F)g2S, and a1b3-v2(G32R)g2S receptor currents.Fourth, a deletion mutation in b3 subunit of the GABAA receptor is present in Angelman Syndrome, in whichabsence-like epilepsy is present.The fifth line of evidence supporting a pathogenic role for the P11S, S15F, and G32R mutations in absence seizures concerns GABRB3 homozygous null mice that have absence-like episodes. GABRB3 heterozygous null mice likewise show frequent absence-like arrests of movement with simultaneous theta bursts, suggesting an insufficient inhibition in the thalamocortical network.In GABRB3-deficient mice, ethosuximide stops seizures and CBZ aggravates seizures,52 the same pharmacological characteristics as those seen in human absence seizures.GABRB3, therefore, plays an important role in the thalamocortical network, which underlies absence seizures.51,53 Voltage-clamp recordings of reticular neurons and ventrobasal neurons of thalamic slices in GABRB3 homozygous null mice show nearly abolished GABA-mediated inhibition in the reticular nucleus. GABA-mediated inhibition was unaffected in ventrobasal relay neurons. Oscillatory synchrony dramatically increases, showing that the recurrent inhibitory connections in the reticular nucleus, whichare lost in the GABRB3 null mice, actually result in desynchronization.