Altered calcium signaling in the granule cell layer of ataxic mutant mice

Lamont, Matthew G. (2014) Altered calcium signaling in the granule cell layer of ataxic mutant mice. Masters thesis, Memorial University of Newfoundland.

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Abstract

The waddles mouse is characterized by a namesake waddling “side-to-side” gait, which is the result of a deficiency in the enzyme carbonic anhydrase type 8 known to inhibit the binding of inositol 1,4,5-trisphosphate to receptors on intracellular calcium stores. Behavioral experiments were conducted utilizing a rota-rod apparatus to further characterize this ataxia. The results indicated the homozygotes performed significantly worse than heterozygotes or wild type animals, and that younger homozygotes outperformed older cohorts. To elucidate potential alterations in cellular calcium signaling, acute cerebellar slices from the vermis were harvested for calcium imaging experiments in vitro. These experiments revealed significant alterations in granule cell somatic calcium signaling in waddles mice. I propose that cerebellar calcium signalling is altered in waddles mice, and that these alterations may be contributing to the observed ataxia through developmental mechanisms. These results will aid in understanding ataxias whose pathological basis involves alterations in neuronal calcium signaling.

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