Unravelling the behavioural and molecular hallmarks of Spinocerebellar Ataxia type 17 (SCA17). Studies on a transgenic rat model

Background: Measuring anxiety in a reliable manner is essential for behavioural phenotyping of rodent models such as the rat model for Spinocerebellar ataxia type 17 (SCA17) where anxiety is reported in patients. An automated tool for assessing anxiety within the home cage can minimize human intervention, stress of handling, transportation and novelty. New method: We applied the anxiety test “light spot” (LS) (white led directed at the food-hopper) to our transgenic SCA17 rat model in the PhenoTyper 4500® to extend the knowledge of this automated tool for behavioural phenotyping and to verify an anxietylike phenotype at three different disease stages for use in future therapeutic studies. Results: Locomotor activity was increased in SCA17 rats at 6 and 9 months during the first 15 minutes of the LS, potentially reflecting increased risk assessment. Both genotypes responded to the test with lower duration in the LS zone and higher time spent inside the shelter compared to baseline. Comparison with existing methods: We present the first data of a rat model subjected to the LS. The LS can be considered more biologically relevant than a traditional test as it measures anxiety in a familiar situation. Conclusions: The LS successfully evoked avoidance and shelter-seeking in rats. SCA17 rats showed a stronger approach-avoidance conflict reflected by increased activity in the area outside the LS. This home cage test, continuously monitoring preand posteffects, provides the opportunity for in-depth analysis, making it a potentially useful tool for detecting subtle or complex anxiety-related traits in rodents.