Functional correlation of GABA(A) receptor α subunits expression with the properties of IPSCs in the developing thalamus

Abstract

GABA(A) receptor α1 and α2 subunits are expressed differentially with ontogenic period in the brain, but their functional roles are not known. We have recorded GABA(A) receptor-mediated IPSCs from laterodorsal (LD) thalamic relay neurons in slices of rat brain at various postnatal ages and found that decay times of evoked IPSCs and spontaneous miniature IPSCs undergo progressive shortening during the first postnatal month. With a similar time course, expression of transcripts and proteins of GABA(A) receptor α2 subunit in LD thalamic region declined, being replaced by those of α1 subunit. To further address the causal relationship between a subunits and IPSC decay time kinetics, we have overexpressed GABA(A) receptor α1 subunit together with green fluorescent protein in LD thalamic neurons in organotypic culture using recombinant Sindbis virus vectors. Miniature IPSCs recorded from the LD thalamic neurons overexpressed with α1 subunit had significantly faster decay time compared with control expressed with β-galactosidase. We conclude that the α2-to-α1 subunit switch underlies the developmental speeding in the decay time of GABAergic IPSCs.