Differential regulation of GABA A receptor subunit mRNAs in rat cerebellar granule neurons: importance of environmental cues.

Levels of the GABA A receptor alpha1-, alpha6-, beta2-, beta3-, gamma2-, and delta-subunit mRNAs in cerebellar granule neurons rise concurrently during the second week of postnatal ontogeny. Previous studies in culture have suggested that extrinsic signals control these increases, but little is known about the nature of the regulatory cues. To determine when granule neurons become competent to express these six subunit mRNAs in mature patterns and to gain insight into their regulation, reverse transcriptase-PCR was used to examine transcript expression in cultured granule neurons prepared at 2-day intervals from postnatal days 2 through 10. Although only one pattern of expression was observed in vivo, three patterns were detected in culture. First, the levels of the alpha1- and alpha6-subunit mRNAs were constant in cultures prepared at all ages. Second, the levels of the beta2-, beta3-, and gamma2-subunit mRNAs were constant in cultures prepared at postnatal days 2-6 but increased in those prepared at days 8-10. Third, the delta-subunit mRNA level increased over time in culture regardless of cerebellar age at plating. Moreover, only delta-subunit transcript expression was modulated by cell density. These findings indicate that the subunit transcripts are differentially regulated by multiple environmental cues.