Figure 6. Performance on the accelerating rotarod varies with sex and Gabrb3 and depends on GABAAR β3 expression only in Purkinje cells.
(A) Latency to fall vs. training day for Gabrb3 P22 males (left) and females (right). (B) Change in latency, calculated as the difference between the Day-1 fall latency and mean Day 5–7 fall for all four groups. Symbol color code as in (A). (C) Latency to fall vs. training day for P22 Purkinje-specific Gabrb3 P22 males (left) and females (right). (D) Change in latency, calculated as the difference between the Day-1 fall latency and mean Day 5–7 fall for Purkinje-specific Gabrb3 mice. Symbol color code as in (C). (E) Change in the rotation rate (in rpm) at which the mouse fell on Day-1 vs. mean Day 5–7 for global Gabrb3 mice (closed symbols) and Purkinje-specific Gabrb3 mice (open symbols).
Figure 6—figure supplement 1. Mouse weight does not account for differences in motor learning.
Weight of Gabrb3 mice (closed symbols) and Purkinje-specific Gabrb3 mice (open symbols) on or immediately after Day 7 of rotarod testing. For Gabrb3 mice, females were lighter than males (+/+ males 16.5 ± 0.7 g, +/+ females 11.6 ± 0.6 g, p<0.001), but mutant males weighed the same as wild-type males (m/p+ males 17.5 ± 0.5 g, p=0.61 vs. +/+ males), and mutant females weighed the same as wild-type females (m/p+ females 13.2 ± 0.4 g, p=0.23 vs. +/+ females). No differences in weight were found between Purkinje-specific Gabrb3 groups (p=0.49).
Figure 6—figure supplement 2. Differences in performance on rotarod change over development.
(Top: ) Average latency to fall on Day 1 for all four age groups for males (left) and females (right). Only m-/p+ females showed variable day 1 latencies throughout development. (Bottom: ) Average Δ latency for all four age groups for males (left) and females (right). Mutant males showed a decreasing Δ latency over development, whereas mutant females showed a increasing Δ latency over development. For all groups (sex, mutation, age), n=8.
Figure 6—figure supplement 3. Selection of rotarod protocols that permit an increase in fall latency over training for transgenic mice on a 129S background.
(A) Change latency to fall on the accelerating rotarod for Purkinje-specific Gabrb3 mice, age P22, subjected to 2 daily trials with the rod accelerating to 30 rpm over 4 min. None of the four groups increased their fall latency over the course of 7 days. (B) Latency to fall for individual Purkinje-specific Gabrb3 +/+ male and female mice on the accelerated rotarod, where the rate of acceleration was reduced to 25 rpm over 4 min, and the number of daily trials was increased to 5. This alteration in the protocol did not result in an increased fall latency on the accelerated rotarod task. (C) Latency to fall on the accelerating rotarod on Day 1 across various acceleration protocols. Mice from all groups are pooled. The rate of acceleration for each protocol is listed in the table (right). The highest acceleration gave the shortest initial latency to fall, but made it possible for mice to improve with training.