Mice Lacking Ataxin-1 Display Learning Deficits and Decreased Hippocampal Paired-Pulse Facilitation

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Abstract
Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. To investigate SCA1 pathogenesis and to gain insight into the function of theSCA1gene product ataxin-1, a novel protein without homology to previously described proteins, we generated mice with a targeted deletion in the murineSca1gene. Mice lacking ataxin-1 are viable, fertile, and do not show any evidence of ataxia or neurodegeneration. However,Sca1null mice demonstrate decreased exploratory behavior, pronounced deficits in the spatial version of the Morris water maze test, and impaired performance on the rotating rod apparatus. Furthermore, neurophysiological studies performed in area CA1 of the hippocampus reveal decreased paired-pulse facilitation inSca1null mice, whereas long-term and post-tetanic potentiations are normal. These findings demonstrate that SCA1 is not caused by loss of function of ataxin-1 and point to the possible role of ataxin-1 in learning and memory.