Harmaline-induced changes in gamma aminobutyric acid A receptor subunit mRNA expression in murine olivocerebellar nuclei

Abstract

Increased CNS activity in the form of electrically or chemically induced seizures is known to alter the properties of GABA A receptors. The tremorgen, harmaline, causes a bursting pattern of activity in inferior olivary neurons, the effects of which are transmitted throughout the olivocerebellar circuit to other regions of the CNS. In situ hybridization was used to determine the effect of this increased activity on gamma aminobutyric acid A (GABA A) receptor subunit gene expression in the cerebellar Purkinje cell layer, deep cerebellar nuclei and inferior olivary complex of adult mice. In Purkinje cells, the expression of α 1, β 2, and γ 2 mRNAs was increased only slightly (<5%) by harmaline administration, while in deep cerebellar neurons, β 2 transcript levels were initially elevated (26%), but dropped to control levels immediately thereafter. The expression of α 2, α 4, β 3 and γ 1 mRNAs in olivary neurons was affected differentially by harmaline administration. The α 4 transcript was increased, reaching >60% above control levels at 6 h post-injection. A smaller increase was observed for α 2 mRNA, while β 3 and γ 1 transcripts dropped below control levels during the same period. The expression of corticotropin-releasing factor mRNA was also elevated in the olivary complex. These data indicate that while Purkinje cells and deep cerebellar neurons are only minimally affected, harmaline induced changes in cellular properties may result in increased numbers of α 4-containing, diazepam-insensitive, GABA A receptors in olivary neurons.