GABA Receptor Expression in the Forebrain of Ataxic Mice.

The human CACNA1A gene encodes the pore-forming α subunit of Ca2.1 (P/Q-type) calcium channels and is the locus for several neurological disorders, including episodic ataxia type 2 (EA2), spinocerebellar ataxia type 6 (SCA6) and Familial Hemiplegic Migraine type 1 (FHM1). Several spontaneous mouse Cacna1a mutant strains exist, among them (), carrying the R1262G point mutation in the mouse Cacna1a gene. mice display a phenotype of severe gait ataxia and motor dysfunction of the hind limbs. At the functional level, the R1262G mutation results in a positive shift of the activation voltage of the Ca2.1 channel and reduced current density. γ-Aminobutyric acid type A (GABA) receptor subunit expression depends critically on neuronal calcium influx, and GABA receptor dysfunction has previously been described for the cerebellum of and other ataxic Cacna1a mutant mice. Given the expression pattern of Ca2.1, it was hypothesized that calcium dysregulation in might affect GABA receptor expression in the forebrain. Herein, functional GABA receptors in the forebrain of mice were quantified and pharmacologically dissociated using [H] radioligand binding. No gross changes to functional GABA receptors were identified. Future cell type-specific analyses are required to identify possible cortical contributions to the psychomotor phenotype of mice.