Modulation of GABA_A Receptor Subunit mRNA Levels in Olivocerebellar Neurons of Purkinje Cell Degeneration and Weaver Mutant Mice

Abstract

Abstract:In olivocerebellar circuits, changes in the subunit composition of GABA A receptors occur at a time of extensive synaptic remodeling. In the deep cerebellar nuclei, GABA A receptor ␣ 1 , ␤ 2 , and ␥ 2 subunit mRNA expression increases throughout neonatal development, whereas in the inferior olivary complex, the perinatal combination of ␣ 3 , ␣ 5 , ␤ 3 , and ␥ 2 mRNAs switches to the adult combination of ␣ 2 , ␣ 4 , ␤ 3 , and ␥ 1 during postnatal week 2. In situ hybridization was used to examine changes in subunit expression in the olivocerebellar nuclei of Purkinje cell degeneration and weaver mutant mice. In Purkinje cell degeneration, subunit transcripts decreased below control levels in olivary neurons; however, ␣ 1 , ␤ 2 , and ␥ 2 transcript levels were slightly increased in the medial nucleus of the deep cerebellar nuclei. In weaver olivary neurons, although the switch from early-to late-onset subunit mRNAs occurred as in normal mice, transcript levels were differentially modulated by the mutation. Our studies indicate that major alterations in synaptic connectivity do not prevent developmentally programmed switches in GABA A receptor gene expression but can modulate the timing and level of transcript expression in afferent and efferent neurons. Key Words: Inferior olive -Deep cerebellar nuclei-pcd/ pcd mice -wv/wv mice -GABA A .

Mutation-related differences in exploratory, spatial, and depressive-like behavior in pcd and Lurcher cerebellar mutant mice

“…The pcd mutation exists in several different alleles (Wang and Morgan, 2007 ). Pcd mice carrying the original allele Agtpbp1 pcd have been used for experiments, e.g., in B6.BR (Vinueza Veloz et al, 2014 ), C57BL/6J (Zhang et al, 1996 ), or B6C3Fe (Rotter et al, 2000 ) strains.…”