DEVELOPMENTAL EXPRESSION OF THE ALPHA-6 GABA-A RECEPTOR SUBUNIT MESSENGER-RNA OCCURS ONLY AFTER CEREBELLAR GRANULE CELL-MIGRATION

Using a competitive polymerase chain reaction (PCR) and appropriate internal standards, we have analyzed absolute amounts of the alpha6 GABA(A) receptor subunit mRNA in the postnatally developing cerebellum and neocortex. The PCR data have shown that absolute amounts of the alpha6 receptor subunit mRNA in the cerebellum increase dramatically (nearly 100-fold) during the second postnatal week, reaching maximal levels by postnatal day 21 (I fmol/mug total RNA). The absolute amount of the alpha6 GABA(A) receptor subunit mRNA in the cortex at postnatal day 1 was 2 amol/mug total RNA and increased to 7 amol/mug total RNA by postnatal day 14. No further increase in alpha6 mRNA expresion in the adult cortex was observed. Microscopic analysis of emulsion coated and counterstained sections indicated that alpha6 GABA(A) receptor subunit mRNA labeling was only detected in the internal granule cell layer and not in either the external granule cell layer or in migrating granule cells. The alpha1 GABA(A) receptor subunit mRNA increased in the cerebellar cortex with a similar temporal profile, although its distribution extended to additional cell types (Purkinje cells, stellate/basket cells and possibly cerebellar astrocytes). The temporal expression of these two GABA(A) receptor subunit mRNAs is coincident with the formation of synaptic contacts in the granule cell dendrites suggesting that afferent pathways innervating these neurons following cell migration may play a critical role in increasing the expression of mRNAs encoding the alpha1 and alpha6 GABA(A) receptor subunits.