Figure 7: Motor coordination and motor learning defects in Cdc42ep4^−/− mice.

(a; Top) Set-up for the balance beam test. The height (0.5 m above the floor) and illumination (100 lux) motivate mice to escape by traversing along a horizontal rod (1 m × 28 or 11 mm) into a dark box. (Bottom) The learning curves of a cohort of WT and KO mice measured at 3 and 6 months of age. The moving speeds are plotted for seven trials with a 28-mm rod and subsequent five trials with an 11-mm rod over 4 days. The motor coordination defects in KO mice remained uncompensated up to 6 months of age (n=13/13 and 12/12, P=0.0003, 0.0004, 0.018, 0.014 by two-way repeated measures ANOVA). (b) The learning curves of 6-week-old WT and KO littermate mice assessed by the rota-rod test before and after direct cerebellar cortical injection of CTZ plus DL-TBOA (100 μM each per 10 μl). The local inhibition of EAATs with the subthreshold dose of DL-TBOA elicited a significant motor coordination defects transiently (around 4 h post-injection) and only in KO mice (n=5/4, P=0.551, 0.0011, 0.957, 0.518 by two-way repeated measures ANOVA). The aberrant hypersensitivity of KO mice indicates their glutamate clearance deficit that is adaptively compensated.