The puzzle box task was performed 7 weeks after injury as described previously (37, 42). The task assesses various domains of cognitive function, including short- and long-term memory and problem solving. Briefly, mice were acclimated to the brightly lit behavioral testing room for 10 min on each of the three consecutive testing days. On each day, mice performed three trials (37). For each trial, mice were placed in the brightly lit start box and required to solve tasks of increasing difficulty to enter a darkened goal box. The trials on the first day served as habituation trials. On trial 1, the underpass to the goal box was clear and there was an open door to the goal box. On trials 2 and 3, the underpass was clear, but there was no longer a door; therefore, mice had to go under the partition and through the underpass to enter the goal box. This was repeated the next day on trial 4. Trial 5 required mice to dig through bedding in the underpass, and this was repeated for trial 6 and again the next day for trial 7. On trial 8, mice were introduced to a cardboard plug that they were required to remove from the underpass to enter the goal box. This was repeated for trial 9. All trials were marked complete once the animal’s hind paws entered the goal box or after a maximum of 7 min. Mice were excluded from the study if it took them more than 3.5 min to complete any of the habituation trials on the first day.

The foot fault task was performed 5 weeks after injury to assess motor function. Mice were acclimated to the behavior room for 10 min before testing. Mice were placed on an enclosed wire grid and were free to explore for 3 min. A blinded observer watched the recorded tests and scored the mice based on the number of times their forepaws slipped through the wire grid. The percent fault difference was calculated as the number of slips per total steps with the right paw minus the number of slips/total steps with the left paw multiplied by 100.

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