GABAA receptor messenger RNA expression in the deep cerebellar nuclei of Purkinje cell degeneration mutants is maintained following the loss of innervating Purkinje neurons

Recent studies have suggested that innervation modulates GABAA receptor gene expression in the rodent cerebellum. To examine this question, the expression and levels of GABAA receptor subunit messenger RNAs in the deep cerebellar nuclei of Purkinje cell degeneration mice and littermate controls were examined by quantitative in situ hybridization histochemistry. In the Purkinje cell degeneration mutant, the selective postnatal degeneration of Purkinje neurons disrupts GABAergic input from the cerebellar cortex to the deep nuclei. Despite this loss of Purkinje cells, virtually all large neurons of the deep cerebellar nuclei of Purkinje cell degeneration animals expressed the alpha 1, beta 2, and gamma 2 subunit messenger RNAs. These subunit messenger RNAs were observed at all experimental times from postnatal day 24 to postnatal day 90, a period ranging from the onset of behavioral abnormalities in the mutant to the completion of Purkinje cell loss. At no time were additional beta subunit messenger RNAs, normally absent from the deep cerebellar nuclei in control mice, detected in this region of the mutant. Quantitative analysis of the hybridization signals over individual neurons revealed that Purkinje cell loss differentially affected the expression of GABAA receptor subunit messenger RNAs. While the levels of the beta 2 and gamma 2 subunit messenger RNAs in individual neurons were comparable in mutants and controls at all ages, differences in alpha 1 subunit messenger RNA expression were observed. At postnatal day 24, the level of alpha 1 subunit mRNA in individual neurons of the mutant was only 60% that found in the control. At later stages (postnatal day 60 to postnatal day 90), the levels of alpha1 subunit messenger RNA expression increased in the mutant, and similar grain densities were detected over mutant and control neurons. These studies demonstrate that Purkinje cell innervation is not required to maintain the expression of messenger RNAs encoding the alpha1, beta2 and gamma 2 GABAA receptor subunits in the deep cerebellar nuclei of the Purkinje cell degeneration mutant. However, Purkinje cell input appears to selectively modulate the level of the alpha1 subunit messenger RNA, suggesting that GABAA receptor genes are differentially regulated.