Modulation of GABA(A) receptor subunit mRNA levels in olivocerebellar neurons of purkinje cell degeneration and weaver mutant mice.
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 alpha1, beta2, and gamma2 subunit mRNA expression increases throughout neonatal development, whereas in the inferior olivary complex, the perinatal combination of alpha3, alpha5, beta3, and gamma2 mRNAs switches to the adult combination of alpha2, alpha4, beta3 and gamma1 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, alpha1, beta2, and gamma2 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.