Uncoupling of GABAA/benzodiazepine receptor alpha 1, beta 2, and gamma 2 subunit mRNA expression in cerebellar Purkinje cells of staggerer mutant mice

Abstract

The mammalian GABAA/benzodiazepine (GABAA/BZ) receptor is comprised of several subunit isoforms: alpha 1-6, beta 1-13, gamma 1-3 and delta. In the present studies, the expression of alpha 1, beta 2, and gamma 2 subunit mRNAs was examined in cerebellar Purkinje cells and deep cerebellar neurons of staggerer mutant mice during postnatal development. In control animals, the three subunit mRNAs were present at high density in Purkinje cells which, in adult animals, form a monolayer at the interface of the granule cell and molecular layers. The number of Purkinje cells in the staggerer cerebellar cortex is reduced; the majority of those that remain are retained within the granule cell layer and are unable to receive normal afferent synapses from granule cells. The three subunit mRNAs were ex pressed at similar levels in both staggerer and control Purkinje cells until postnatal day 9. After this time, although the alpha 1 subunit mRNA was maintained at control levels in staggerer Purkinje cells, the expression of beta 2 and gamma 2 subunit mRNAs decreased, and was largely absent by postnatal day 20. The loss of beta 2 and gamma 2 mRNA expression in staggerer was specific to Purkinje cells, since all three mRNAs were present throughout postnatal development in other brain regions, including the deep cerebellar nuclei. The present studies indicate that in cerebellar Purkinje cells, the GABAA/BZ receptor alpha 1, and beta 2, and gamma 2, subunit mRNAs are regulated by distinct mechanisms which are differentially affected by the staggerer mutation.