Temporal modulation of GABA(A) receptor subunit gene expression in developing monkey cerebral cortex.

Abstract

In situ hybridization histochemistry was used to examine the expression of 10 GABA(A) receptor messenger RNAs corresponding to the alpha1-alpha5, beta1-beta3, gamma1 and gamma2 subunits in primary somatosensory and visual areas of macaque monkey cerebral cortex from embryonic day (E) 125 to postnatal day (P) 125. Results were compared with expression patterns in adults. In the sensorimotor cortex at E125, overall levels of all subunit transcripts were low. At E137, there was a major lamina-specific increase in all subunit messenger RNAs except gamma1. For alpha1, alpha2, alpha4, beta2, beta3 and gamma2 subunit transcripts, this increase was highest in areas 3a and 3b, particularly in layers III/IV and VI. Postnatally, there were significant decreases in all transcripts. Alpha1, alpha5, beta2 and gamma2 subunit transcripts, while still at significantly lower levels than at E137, remained expressed at levels higher than other transcripts. Unlike in rodents, there was no obvious "switch" in the major subunits expressed in fetal and adult cortex, alpha1, alpha5, beta2 and gamma2 remaining highest throughout. In area 17, the most prominently expressed subunits at earliest ages were alpha2, alpha5, beta1, beta2, beta3 and gamma2, especially in layers II/III and VI. At E150, expression for alpha2, alpha3, beta1 and beta3 subunit transcripts in these layers decreased, but levels for alpha1, alpha4, alpha5, beta2, gamma1 and gamma2 transcripts increased, particularly within layer IV. The increase at E150 was particularly marked for alpha5 transcripts, which were expressed at levels more than four times those of other transcripts. Alpha1, beta2 and gamma2 remain highest into aduthood. Fetal area 17 displayed lamina-specific patterns of expression not found in adult animals. In particular, alpha3 messenger RNAs were present in layer IVA and gamma1 transcripts were present in layer IVC at E150, despite a lack of expression in these layers in the adult. These data demonstrate increased expression of GABA(A) receptors during the period of establishment of thalamocortical and intracortical connections, and a temporal regulation that may be associated with the period of developmental plasticity.